Metabolic Syndrome
Conditions
Keywords
metabolic syndrome, eye, cardiometabolic, Cornelian Cherry, natural extracts, iridoids
Brief summary
This randomized, double-blind, placebo-controlled, parallel-group study evaluated the effects of six-month oral supplementation with Cornus mas fruit lyophilizate in patients with metabolic syndrome. Participants were assigned to receive either 8 g of Cornus mas fruit lyophilizate once daily or a matching placebo. Ophthalmic assessments included best-corrected visual acuity, slit-lamp examination, dilated fundus examination, applanation tonometry, and Doppler ultrasonography of the ophthalmic, central retinal, and posterior ciliary arteries. Cardiometabolic and biochemical parameters were also assessed at baseline and after 3 and 6 months of supplementation.
Detailed description
This was a randomized, double-blind, placebo-controlled, parallel-group dietary intervention study conducted in patients with metabolic syndrome. Participants were randomly assigned to receive either 8 g of Cornus mas L. fruit lyophilizate once daily or a matching placebo for 6 months. The study aimed to evaluate the effects of Cornus mas supplementation on ophthalmic, vascular, cardiometabolic, and biochemical parameters. Ophthalmic examinations included best-corrected visual acuity for distance and near, slit-lamp biomicroscopy, dilated fundus examination, applanation tonometry, and Doppler ultrasonography of the ophthalmic artery, central retinal artery, and posterior ciliary artery. Cardiometabolic assessments included anthropometric measurements, 24-hour ambulatory blood pressure monitoring, oral glucose tolerance testing, insulin measurements, and serum lipid profile. Selected circulating biomarkers related to oxidative stress, inflammation, advanced glycation, and ocular physiology were also assessed. Study assessments were performed at baseline, after 3 months, and after 6 months of supplementation. In the second phase, the investigators will analyse samples of frozen blood and faeces previously collected from patients. The second phase will run from 1 August 2026 to 31 December 2026.
Interventions
DIETARY_SUPPLEMENTPlacebo
A matching placebo formulation containing potato starch and sugar but no Cornus mas fruit lyophilizate, administered orally once daily for 6 months as a preparation made into a jelly.
DIETARY_SUPPLEMENTCornus mas Fruit Lyophilizate
A dietary supplement containing 8 g of lyophilized whole Cornus mas L. fruit, administered orally once daily for 6 months as a powder or granulate formulation prepared as a jelly.
Sponsors
Wroclaw Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomized intervention
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 and 70 years * Metabolic syndrome defined as central obesity, with a waist circumference of ≥94 cm in men or ≥80 cm in women, and at least two of the following: * Fasting triglyceride concentration ≥1.7 mmol/L * Low high-density lipoprotein cholesterol concentration: \<1.03 mmol/L in men or \<1.29 mmol/L in women * Elevated blood pressure: systolic blood pressure ≥130 mmHg and diastolic blood pressure ≥85 mmHg * Fasting glucose concentration ≥6.5 mmol/L * Best-corrected visual acuity of 20/40 or better * Spherical refractive error between -4.0 and +4.0 diopters * Cylindrical refractive error between -3.0 and +3.0 diopters
Exclusion criteria
* Current smoking * Insulin-dependent diabetes mellitus * Liver disease * Gastrointestinal disease * Cancer * Inflammatory disease * Use of weight-loss medication * Use of anti-inflammatory medication * Pregnancy * Breastfeeding * Alcohol or drug abuse * Requirement to follow a medically prescribed diet other than the diet recommended for metabolic syndrome * Hypotension * Severe circulatory failure * Vascular endothelial abnormalities that could affect blood flow to the optic nerve head * Ocular surgery within 12 months before enrollment * Age-related macular degeneration * Diabetic retinopathy * Retinal vein occlusion * Glaucoma * Other serious acquired or hereditary ocular disease * Neurological disorder that could interfere with ophthalmological examinations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| An SHBG (sex hormone-binding globulin) test | Baseline, 3 months, and 6 months | An SHBG (sex hormone-binding globulin) test is a blood test that measures the concentration of a protein which transports hormones (mainly testosterone and oestradiol) and regulates their levels in the body. It helps doctors determine what proportion of the hormones is bound (inactive) and what proportion is biologically active. |
| cortisol test | Baseline, 3 months, and 6 months | A cortisol test measures the level of the so-called 'stress hormone', which is produced by the adrenal glands. It is used to assess adrenal function and helps to diagnose serious hormonal disorders, such as Cushing's syndrome (excess) or Addison's disease (deficiency). |
| The 25(OH)D3 test | Baseline, 3 months, and 6 months | The 25(OH)D3 test, which measures the concentration of 25-hydroxyvitamin D in the blood, is the most accurate indicator of vitamin D levels in the body. It enables the detection of deficiencies or excesses, which is crucial for, amongst other things, bone health and immunity. |
| A parathyroid hormone (PTH) | Baseline, 3 months, and 6 months | A parathyroid hormone (PTH) test is a blood test that measures the level of a hormone produced by the parathyroid glands. It is crucial for diagnosing disorders of calcium and phosphate metabolism (e.g. osteoporosis, kidney stones or kidney disease) and abnormalities in the functioning of the parathyroid glands themselves (hyperparathyroidism or hypoparathyroidism). |
| plasma renin activity | Baseline, 3 months, and 6 months | ARO stands for plasma renin activity. This blood test measures the concentration and activity of renin - an enzyme produced by the kidneys. It helps doctors diagnose and manage high blood pressure and adrenal gland disorders, particularly when combined with a measurement of aldosterone levels. |
| An aldosterone test | Baseline, 3 months, and 6 months | An aldosterone test is a blood or urine test that measures the level of aldosterone - a hormone produced by the adrenal glands. This hormone regulates water and electrolyte balance by retaining sodium and water in the body and facilitating the excretion of potassium. The test is crucial in diagnosing high blood pressure (particularly treatment-resistant hypertension) and disorders of the kidneys and adrenal glands. |
| Adipokine tests | Baseline, 3 months, and 6 months | Adipokine tests are blood tests that measure the levels of hormones and signalling molecules (known as adipokines) produced by adipose tissue. The most important of these are adiponectin and leptin. They enable the assessment of the risk of metabolic syndrome and type 2 diabetes, as well as the degree of insulin resistance. |
| An FMD (Flow-Mediated Dilation) ultrasound scan | Baseline, 3 months, and 6 months | An FMD (Flow-Mediated Dilation) ultrasound scan is a non-invasive test used to assess the condition of the circulatory system, and more specifically the function of the vascular endothelium - the thin layer of cells lining the inside of blood vessels. It is a key indicator for detecting the early stages of atherosclerosis. |
| ABPM (Ambulatory Blood Pressure Monitoring) | Baseline, 3 months, and 6 months | ABPM (Ambulatory Blood Pressure Monitoring), commonly known as a blood pressure Holter monitor, is a 24-hour (or longer) automated monitoring of blood pressure. It enables an assessment of how blood pressure changes during daily activities, at work, whilst sleeping and in stressful situations. |
| Bioimpedance analysis (BIA) | Baseline, 3 months, and 6 months | Bioimpedance analysis (BIA) is a quick and painless test that allows you to find out exactly what your body is made of. Instead of just your overall weight, you receive precise information about the proportions of muscle, fat and water in your body. |
| Densitometry | Baseline, 3 months, and 6 months | Densitometry is a non-invasive and painless X-ray examination used to assess bone mineral density (BMD). It is a key test for the early detection of osteopenia and osteoporosis, as well as for assessing the risk of bone fractures. |
| A urine test | Baseline, 3 months, and 6 months | A urine test is a basic and non-invasive laboratory test that assesses the functioning of the kidneys, the urinary tract and the body as a whole. It helps with the early detection of, amongst other things, infections, diabetes, liver disease and metabolic disorders |
| a stool test | Baseline, 3 months, and 6 months | A stool test is a non-invasive laboratory analysis of a stool sample, which enables the assessment of digestive system function, the detection of parasites, bacteria and viruses, and the identification of inflammation, bleeding or malabsorption. It is a key tool in the diagnosis of, amongst other things, diseases of the intestines, pancreas and liver. |
| the visual field test | Baseline, 3 months, and 6 months | A visual field test (perimetry) is a painless eye test that measures the extent of the area visible to the eye whilst it is fixed on a single point. It helps to detect blind spots and assess the condition of the retina, the optic nerve and the nerve pathways in the brain. |
| A visual acuity test | Baseline, 3 months, and 6 months | A visual acuity test is a basic ophthalmological and optometric test that assesses the eye's ability to clearly recognise shapes and details. It involves reading letters, numbers or symbols (optotypes) of various sizes from a specific distance, usually using a Snellen chart or a projector |
| An intraocular pressure test | Baseline, 3 months, and 6 months | An intraocular pressure test (tonometry) measures the pressure of the fluid inside the eyeball. It helps to detect dangerous conditions (such as glaucoma) before they cause damage to your eyesight. Normal values range from 10 to 21 mm Hg. The test is painless and takes just a few seconds. |
| Periorbital blood flow assessment | Baseline, 3 months, and 6 months | Periorbital blood flow assessment (often performed as an orbital Doppler ultrasound) is a non-invasive ultrasound technique used in ophthalmology to assess the velocity, direction and quality of blood flow in the blood vessels supplying the eye. |
| biomicroscopy | Baseline, 3 months, and 6 months | Examination of the anterior segment of the eye using a slit lamp - biomicroscopy assessment of, amongst other things, the conjunctiva, cornea, anterior chamber, iris and lens. |
| funduscopy | Baseline, 3 months, and 6 months | Examination of the back of the eye following pupil dilation - funduscopy assessment of the retina, the macula, the optic disc and the retinal vessels. |
| White Blood Cell Count | Baseline, 3 months, and 6 months | White blood cell count measured in peripheral venous blood using an automated hematology analyzer. Results will be reported as the mean white blood cell count for each study group. |
| Hematocrit | Baseline, 3 months, and 6 months | Hematocrit measured in peripheral venous blood using an automated hematology analyzer. Results will be reported as the percentage of blood volume occupied by red blood cells. |
| Mean Corpuscular Volume | Baseline, 3 months, and 6 months | Mean corpuscular volume measured in peripheral venous blood using an automated hematology analyzer. Results will be reported as the average volume of red blood cells. |
| Neutrophil Count | Baseline, 3 months, and 6 months | Absolute neutrophil count measured in peripheral venous blood using an automated hematology analyzer. Results will be reported as the number of neutrophils per liter of blood. |
| Lymphocyte Count | Baseline, 3 months, and 6 months | Absolute lymphocyte count measured in peripheral venous blood using an automated hematology analyzer. Results will be reported as the number of lymphocytes per liter of blood. |
| insulin test | Baseline, 3 months, and 6 months | An insulin test is a laboratory blood test that evaluates the body's carbohydrate metabolism and the function of the pancreas. |
| creatinine test | Baseline, 3 months, and 6 months | A creatinine test is the most important and most sensitive laboratory blood test used to assess kidney function and filtration capacity. |
| The OGTT (Oral Glucose Tolerance Test) | Baseline, 3 months, and 6 months | The OGTT (Oral Glucose Tolerance Test), also known as the oral glucose tolerance test (commonly referred to as the glucose curve), is a key diagnostic test used to assess how well the body metabolizes carbohydrates. |
| A fibrinogen test | Baseline, 3 months, and 6 months | A fibrinogen test is a laboratory blood test that assesses the body's ability to clot blood properly and helps detect inflammation |
| Platelet Count | Baseline, 3 months, and 6 months | Platelet count measured in peripheral venous blood using an automated hematology analyzer. Results will be reported as the mean platelet count for each study group. |
| Hemoglobin Concentration | Baseline, 3 months, and 6 months | Hemoglobin concentration measured in peripheral venous blood using an automated hematology analyzer. Results will be reported in grams per deciliter. |
| Red Blood Cell Count | Baseline, 3 months, and 6 months | Red blood cell count measured in peripheral venous blood using an automated hematology analyzer. Results will be reported as the mean red blood cell count for each study group. |
| CRP | Baseline, 3 months, and 6 months | The CRP (C-Reactive Protein) test measures the level of C-reactive protein in blood serum, which is one of the most sensitive and rapidly responding indicators of inflammation in the body. |
| lipid profile | Baseline, 3 months, and 6 months | A lipid profile is a blood test that measures the levels of cholesterol and triglycerides in the body. It is one of the most important preventive tests used to assess the risk of developing cardiovascular diseases, such as atherosclerosis, heart attack, or stroke. |
| urea level test | Baseline, 3 months, and 6 months | A urea level test is a basic blood chemistry test used primarily to assess kidney function and monitor protein metabolism in the body |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Interleukin-8 Concentration | Baseline, 3 months, and 6 months | Serum interleukin-8 (IL-8) concentration will be measured as a chemokine associated with neutrophil recruitment and systemic inflammatory activity. |
| Change in Serum Interleukin-18 Concentration | Baseline, 3 months, and 6 months | Serum interleukin-18 (IL-18) concentration will be measured as a pro-inflammatory cytokine associated with innate and adaptive immune activation. |
| Change in Serum Tumor Necrosis Factor Alpha Concentration | Baseline, 3 months, and 6 months | Serum tumor necrosis factor alpha (TNF-α) concentration will be measured as a marker of systemic pro-inflammatory activity. |
| Change in the Pro-Inflammatory Cytokine Profile | Baseline, 3 months, and 6 months | The systemic pro-inflammatory cytokine profile will be assessed using selected cytokines, including IL-6, IL-15, IL-1α, IL-8, IL-18 and TNF-α. |
| Change in the Anti-Inflammatory Cytokine Profile | Baseline, 3 months, and 6 months | The systemic anti-inflammatory cytokine profile will be assessed primarily using serum IL-10 and other predefined anti-inflammatory cytokines included in the laboratory panel. |
| Change in the Pro-Inflammatory-to-Anti-Inflammatory Cytokine Balance | Baseline, 3 months, and 6 months | Ratios between selected pro-inflammatory cytokines and IL-10 will be calculated as exploratory indicators of the balance between systemic pro-inflammatory and anti-inflammatory activity. |
| Change in Circulating Endothelial Function Marker Concentrations | Baseline, 3 months, and 6 months | Selected circulating markers of vascular endothelial function will be measured in serum or plasma. The panel may include markers of endothelial activation, vascular inflammation, vascular adhesion, angiogenesis and endothelial injury. |
| Change in Soluble Intercellular Adhesion Molecule-1 Concentration | Baseline, 3 months, and 6 months | Serum or plasma soluble intercellular adhesion molecule-1 (sICAM-1) concentration will be measured as a marker of endothelial activation and leukocyte adhesion. |
| Change in Soluble Vascular Cell Adhesion Molecule-1 Concentration | Baseline, 3 months, and 6 months | Serum or plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration will be measured as a marker of endothelial activation and vascular inflammation. |
| Change in E-Selectin Concentration | Baseline, 3 months, and 6 months | Serum or plasma E-selectin concentration will be measured as a marker of endothelial-cell activation. |
| Change in Endothelin-1 Concentration | Baseline, 3 months, and 6 months | Plasma endothelin-1 concentration will be measured as a marker of endothelial vasoconstrictive activity. |
| Change in von Willebrand Factor Concentration | Baseline, 3 months, and 6 months | Plasma von Willebrand factor concentration or activity will be measured as a marker associated with endothelial activation and vascular hemostatic function. |
| Change in Reduced Glutathione Concentration | Baseline, 3 months, and 6 months | Reduced glutathione (GSH) concentration will be measured in blood or erythrocytes as a marker of intracellular antioxidant capacity. |
| Change in Oxidized Glutathione Concentration | Baseline, 3 months, and 6 months | Oxidized glutathione (GSSG) concentration will be measured in blood or erythrocytes as a marker of glutathione oxidation and oxidative stress. |
| Change in the Reduced-to-Oxidized Glutathione Ratio | Baseline, 3 months, and 6 months | The GSH-to-GSSG ratio will be calculated as an indicator of cellular redox balance. A lower ratio may indicate increased oxidative stress. |
| Change in Glutathione Peroxidase Activity | Baseline, 3 months, and 6 months | Glutathione peroxidase (GPx) activity will be measured in blood, erythrocytes or plasma as a marker of enzymatic antioxidant defense. |
| Change in Superoxide Dismutase Activity | Baseline, 3 months, and 6 months | Superoxide dismutase (SOD) activity will be measured in blood, erythrocytes or plasma as a marker of enzymatic antioxidant defense against superoxide radicals. |
| Change in Catalase Activity | Baseline, 3 months, and 6 months | Catalase activity will be measured in blood, erythrocytes or plasma as a marker of enzymatic antioxidant defense against hydrogen peroxide. |
| Change in Total Antioxidant Status | Baseline, 3 months, and 6 months | Total antioxidant status (TAS) will be measured in serum or plasma as an integrated marker of the overall antioxidant capacity of the biological sample. |
| Change in Trolox Equivalent Antioxidant Capacity | Baseline, 3 months, and 6 months | Trolox equivalent antioxidant capacity (TEAC) will be measured in serum or plasma as an estimate of the total non-enzymatic antioxidant capacity. Results will be expressed as Trolox equivalents. |
| Change in Protein Carbonyl Concentration | Baseline, 3 months, and 6 months | Protein carbonyl concentration will be measured in serum, plasma or other selected biological material as a marker of oxidative protein damage and protein carbonylation. |
| Change in F2-Isoprostane Concentration | Baseline, 3 months, and 6 months | F2-isoprostane concentration will be measured in plasma, serum or urine as a marker of lipid peroxidation and systemic oxidative stress. |
| Change in Selected Nitrosative Stress Marker Concentrations | Baseline, 3 months, and 6 months | Selected markers of nitrosative stress will be measured in the predefined biological material. The analysis may include nitric oxide metabolites, nitrotyrosine or other validated indicators of reactive nitrogen species-mediated damage. |
| Change in 3-Nitrotyrosine Concentration | Baseline, 3 months, and 6 months | Serum or plasma 3-nitrotyrosine concentration will be measured as a marker of protein nitration and nitrosative stress. |
| Change in Total Nitrate and Nitrite Concentration | Baseline, 3 months, and 6 months | Total nitrate and nitrite concentration will be measured in serum or plasma as an indirect marker of systemic nitric oxide production and metabolism. |
| Change in Fasting Plasma Glucose Concentration | Baseline, 3 months, and 6 months | Fasting plasma glucose concentration will be measured after an overnight fast as a marker of glucose metabolism. Results will be reported in mg/dL or mmol/L. |
| Change in Fasting Serum Insulin Concentration | Baseline, 3 months, and 6 months | Fasting serum insulin concentration will be measured as a marker of pancreatic insulin secretion and insulin metabolism. Results will be reported in µIU/mL, mIU/L or another unit appropriate for the analytical method. |
| Change in Glucose Concentration During the Oral Glucose Tolerance Test | Baseline, 3 months, and 6 months | Plasma glucose concentration will be measured during an oral glucose tolerance test following administration of a standardized oral glucose load. Measurements will be performed at predefined time points, such as fasting and 30, 60, 90 or 120 minutes after glucose administration. |
| Change in Insulin Concentration During the Oral Glucose Tolerance Test | Baseline, 3 months, and 6 months | Serum insulin concentration will be measured at predefined time points during the oral glucose tolerance test to assess the insulin response to oral glucose administration. |
| Change in the Glucose Area Under the Curve During the Oral Glucose Tolerance Test | Baseline, 3 months, and 6 months | The area under the plasma glucose concentration-time curve will be calculated from glucose measurements obtained during the oral glucose tolerance test. |
| Change in the Insulin Area Under the Curve During the Oral Glucose Tolerance Test | Baseline, 3 months, and 6 months | The area under the serum insulin concentration-time curve will be calculated from insulin measurements obtained during the oral glucose tolerance test. |
| Change in the Homeostatic Model Assessment of Insulin Resistance | Baseline, 3 months, and 6 months | The Homeostatic Model Assessment of Insulin Resistance index will be calculated from fasting glucose and fasting insulin concentrations as an estimate of insulin resistance. |
| Change in the Homeostatic Model Assessment of Beta-Cell Function | Baseline, 3 months, and 6 months | The Homeostatic Model Assessment of beta-cell function will be calculated from fasting glucose and fasting insulin concentrations as an estimate of pancreatic beta-cell function. |
| Change in the Matsuda Insulin Sensitivity Index | Baseline, 3 months, and 6 months | The Matsuda index will be calculated from glucose and insulin concentrations measured during the oral glucose tolerance test as an estimate of whole-body insulin sensitivity. |
| Change in the Insulinogenic Index | Baseline, 3 months, and 6 months | The insulinogenic index will be calculated from early glucose and insulin responses during the oral glucose tolerance test as an estimate of early-phase insulin secretion. |
| Change in Serum Total Cholesterol Concentration | Baseline, 3 months, and 6 months | Serum total cholesterol concentration will be measured as a marker of lipid metabolism. Results will be reported in mg/dL or mmol/L. |
| Change in Serum Low-Density Lipoprotein Cholesterol Concentration | Baseline, 3 months, and 6 months | Serum low-density lipoprotein cholesterol concentration will be measured or calculated as a marker of atherogenic lipoprotein metabolism. |
| Change in Serum High-Density Lipoprotein Cholesterol Concentration | Baseline, 3 months, and 6 months | Serum high-density lipoprotein cholesterol concentration will be measured as a marker of reverse cholesterol transport and cardiovascular risk. |
| Change in Serum Non-High-Density Lipoprotein Cholesterol Concentration | Baseline, 3 months, and 6 months | Non-high-density lipoprotein cholesterol will be calculated as total cholesterol minus high-density lipoprotein cholesterol. |
| Change in Serum Triglyceride Concentration | Baseline, 3 months, and 6 months | Serum triglyceride concentration will be measured as a marker of circulating lipid metabolism. |
| Change in the Total Cholesterol-to-High-Density Lipoprotein Cholesterol Ratio | Baseline, 3 months, and 6 months | The ratio of total cholesterol to high-density lipoprotein cholesterol will be calculated as an exploratory marker of cardiovascular risk. |
| Change in the Low-Density Lipoprotein-to-High-Density Lipoprotein Cholesterol Ratio | Baseline, 3 months, and 6 months | The ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol will be calculated as an exploratory marker of atherogenic lipid balance. |
| Change in the Atherogenic Index of Plasma | Baseline, 3 months, and 6 months | The atherogenic index of plasma will be calculated as the logarithm of the ratio of triglycerides to high-density lipoprotein cholesterol, using concentrations expressed in molar units. |
| Change in Serum Apolipoprotein A-I Concentration | Baseline, 3 months, and 6 months | Serum apolipoprotein A-I concentration will be measured as the principal protein component of high-density lipoproteins and a marker of reverse cholesterol transport. |
| Change in Serum Apolipoprotein B100 Concentration | Baseline, 3 months, and 6 months | Serum apolipoprotein B100 concentration will be measured as a marker of the number of circulating atherogenic lipoprotein particles. |
| Change in the Apolipoprotein B100-to-Apolipoprotein A-I Ratio | Baseline, 3 months, and 6 months | The ratio of apolipoprotein B100 to apolipoprotein A-I will be calculated as an exploratory marker of the balance between atherogenic and anti-atherogenic lipoproteins. |
| Change in Serum Apolipoprotein E Concentration | Baseline, 3 months, and 6 months | Serum apolipoprotein E concentration will be measured as a marker associated with lipoprotein transport, lipid clearance and cholesterol metabolism. |
| Change in Oxidized Low-Density Lipoprotein Concentration | Baseline, 3 months, and 6 months | Serum or plasma oxidized low-density lipoprotein concentration will be measured as a marker of oxidative modification of circulating lipoproteins. |
| Change in Lipid Peroxidation Marker Concentrations | Baseline, 3 months, and 6 months | Selected markers of lipid peroxidation will be measured in serum, plasma or urine. The analysis may include malondialdehyde, lipid hydroperoxides, thiobarbituric acid-reactive substances or F2-isoprostanes, depending on the predefined analytical protocol. |
| Change in Serum Leptin Concentration | Baseline, 3 months, and 6 months | Serum leptin concentration will be measured as an adipokine associated with energy balance, appetite regulation and adipose tissue mass. |
| Change in Soluble Leptin Receptor Concentration | Baseline, 3 months, and 6 months | Serum soluble leptin receptor concentration will be measured as a marker of leptin-binding capacity and leptin signaling. |
| Change in the Free Leptin Index | Baseline, 3 months, and 6 months | The free leptin index will be calculated from serum leptin and soluble leptin receptor concentrations as an exploratory indicator of biologically available leptin. |
| Change in Serum Resistin Concentration | Baseline, 3 months, and 6 months | Serum resistin concentration will be measured as an adipokine associated with inflammation and insulin resistance. |
| Change in Serum Nicotinamide Phosphoribosyltransferase Concentration | Baseline, 3 months, and 6 months | Serum nicotinamide phosphoribosyltransferase, also known as visfatin, concentration will be measured as an adipokine and enzyme associated with energy metabolism and inflammation. |
| Change in Serum Omentin Concentration | Baseline, 3 months, and 6 months | Serum omentin concentration will be measured as an adipokine associated with insulin sensitivity and vascular function. |
| Change in Serum Chemerin Concentration | Baseline, 3 months, and 6 months | Serum chemerin concentration will be measured as an adipokine associated with adipogenesis, inflammation and metabolic regulation. |
| Change in Serum Apelin Concentration | Baseline, 3 months, and 6 months | Serum apelin concentration will be measured as an adipokine associated with cardiovascular regulation, glucose metabolism and energy balance. |
| Change in Serum Vaspin Concentration | Baseline, 3 months, and 6 months | Serum vaspin concentration will be measured as an adipokine associated with insulin sensitivity and metabolic regulation. |
| Change in Serum Retinol-Binding Protein 4 Concentration | Baseline, 3 months, and 6 months | Serum retinol-binding protein 4 concentration will be measured as an adipokine associated with insulin resistance and retinol transport. |
| Change in Serum Fatty Acid-Binding Protein 4 Concentration | Baseline, 3 months, and 6 months | Serum fatty acid-binding protein 4 concentration will be measured as a marker of adipocyte function, lipid metabolism and cardiometabolic risk. |
| Change in Serum Interleukin-6 Concentration | Baseline, 3 months, and 6 months | Serum interleukin-6 concentration will be measured as a marker of systemic and adipose tissue-associated inflammation. |
| Change in Serum Monocyte Chemoattractant Protein-1 Concentration | Baseline, 3 months, and 6 months | Serum monocyte chemoattractant protein-1 concentration will be measured as a chemokine associated with monocyte recruitment and adipose tissue inflammation. |
| Change in Plasma Plasminogen Activator Inhibitor-1 Concentration | Baseline, 3 months, and 6 months | Plasma plasminogen activator inhibitor-1 concentration will be measured as a marker associated with impaired fibrinolysis, adipose tissue dysfunction and cardiometabolic risk. |
| Change in Serum Lipocalin-2 Concentration | Baseline, 3 months, and 6 months | Serum lipocalin-2, also known as neutrophil gelatinase-associated lipocalin, concentration will be measured as a marker associated with inflammation, metabolic dysfunction and renal injury. |
| Change in Serum Progranulin Concentration | Baseline, 3 months, and 6 months | Serum progranulin concentration will be measured as an adipokine and inflammatory mediator associated with obesity and insulin resistance. |
| Change in Serum Secreted Frizzled-Related Protein 5 Concentration | Baseline, 3 months, and 6 months | Serum secreted frizzled-related protein 5 concentration will be measured as an adipokine associated with Wnt signaling, inflammation and metabolic homeostasis. |
| Change in Serum Angiopoietin-Like Protein 2 Concentration | Baseline, 3 months, and 6 months | Serum angiopoietin-like protein 2 concentration will be measured as a marker associated with chronic inflammation, adipose tissue dysfunction and vascular disease. |
| Change in Serum Angiopoietin-Like Protein 4 Concentration | Baseline, 3 months, and 6 months | Serum angiopoietin-like protein 4 concentration will be measured as a regulator of lipoprotein lipase activity, triglyceride metabolism and energy homeostasis. |
| Change in Serum Asprosin Concentration | Baseline, 3 months, and 6 months | Serum asprosin concentration will be measured as a fasting-induced glucogenic hormone associated with appetite, hepatic glucose production and insulin resistance. |
| Mean change from baseline in serum alpha-crystallin A (CRYAA) concentration | Baseline, 3 months, and 6 months | Serum alpha-crystallin A (CRYAA) concentration will be measured in stored serum samples using a quantitative enzyme-linked immunosorbent assay (ELISA). For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. Results will be reported in ng/mL. |
| The aldehyde dehydrogenase 1A1 (ALDH1A1) test | Baseline, 3 months, and 6 months | The aldehyde dehydrogenase 1A1 (ALDH1A1) test measures the level of an enzyme that helps remove toxic substances from cells. |
| The carboxymethyllysine (CML) assay test | Baseline, 3 months, and 6 months | The carboxymethyllysine (CML) assay is a test that assesses the level of advanced glycation end products. It serves as a marker of oxidative stress and vascular damage in diabetes, kidney disease and the ageing process |
| The determination of carboxyethyllysine (CEL) concentration | Baseline, 3 months, and 6 months | The determination of carboxyethyllysine (CEL) concentration is used to measure advanced glycation end products (AGEs) in serum or tissues. It helps to assess the extent of protein damage resulting from oxidative stress and ageing processes. |
| The sRAGE (soluble receptor for advanced glycation end-products) test | Baseline, 3 months, and 6 months | The sRAGE (soluble receptor for advanced glycation end-products) test measures the level of a protein in the blood that acts as a 'trap' for harmful sugar molecules and inflammatory substances. |
| The 4-hydroxynonenal (4-HNE) test | Baseline, 3 months, and 6 months | The 4-hydroxynonenal (4-HNE) test is a laboratory analysis of a toxic lipid peroxidation product, used as an indicator of the severity of oxidative stress and cellular damage. |
| AOPP (advanced oxidation protein products) | Baseline, 3 months, and 6 months | AOPP (advanced oxidation protein products) are advanced oxidation products of proteins, which indicate the extent of damage to plasma proteins caused by oxidative stress and inflammation. |
| An interleukin-6 (IL-6) test | Baseline, 3 months, and 6 months | An interleukin-6 (IL-6) test is a standard, widely available laboratory test used to quantify the concentration of this protein molecule (cytokine) in the blood. It helps with the rapid detection and monitoring of acute and chronic inflammatory conditions. |
| The sICAM-1 (soluble intercellular adhesion molecule-1) test | Baseline, 3 months, and 6 months | The sICAM-1 (soluble intercellular adhesion molecule-1) test measures the concentration of a protein that is released into the blood when the endothelium of blood vessels is damaged or stimulated, and by the immune system. |
| An analysis of the composition of the gut flora (microbiome) | Baseline, 3 months, and 6 months | An analysis of the composition of the gut flora (microbiome) is a genetic or microbiological analysis of a stool sample, which involves a quantitative and qualitative assessment of microorganisms. |
| Change in Fecal Calprotectin Concentration | Baseline, 3 months, and 6 months | Fecal calprotectin concentration will be measured in stool samples as a marker of intestinal mucosal inflammation. Results will be reported as the concentration of calprotectin in feces, for example in µg/g of stool. |
| Change in Fecal Lactoferrin Concentration | Baseline, 3 months, and 6 months | Fecal lactoferrin concentration will be measured in stool samples as a marker of neutrophil-associated intestinal inflammation. Results will be reported as the concentration of lactoferrin in feces, for example in µg/g of stool. |
| Mean change from baseline in serum calcium concentration | Baseline, 3 months, and 6 months | Serum calcium concentration will be measured in stored serum samples using a validated clinical chemistry method. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change in Fecal Zonulin Concentration | Baseline, 3 months, and 6 months | Fecal zonulin concentration will be measured as an exploratory marker associated with intestinal barrier function and intestinal permeability. Results will be reported as the concentration of zonulin in feces. |
| Change in Fecal Lipopolysaccharide Concentration | Baseline, 3 months, and 6 months | The concentration of bacterial lipopolysaccharide (LPS) will be measured in stool samples as an exploratory marker of the presence of Gram-negative bacterial components in the intestinal lumen. Results will be reported as the concentration of LPS in feces. |
| Change in Lipopolysaccharide-Binding Protein Concentration | Baseline, 3 months, and 6 months | Lipopolysaccharide-binding protein (LBP) will be measured as a marker associated with host exposure and immune response to bacterial lipopolysaccharides. Results will be reported as the concentration of LBP in the analyzed biological material. |
| Change in Soluble CD14 Concentration | Baseline, 3 months, and 6 months | Soluble CD14 (sCD14) will be measured as a marker associated with innate immune activation and the host response to bacterial lipopolysaccharides. Results will be reported as the concentration of sCD14 in the analyzed biological material. |
| Change in Fecal Alpha-1-Antitrypsin Concentration | Baseline, 3 months, and 6 months | Fecal alpha-1-antitrypsin concentration will be measured as a marker associated with intestinal protein loss and intestinal mucosal barrier integrity. Results will be reported as the concentration of alpha-1-antitrypsin in feces. |
| Change in Fecal Pancreatic Elastase Concentration | Baseline, 3 months, and 6 months | Fecal pancreatic elastase concentration will be measured as a marker of exocrine pancreatic function. Results will be reported in µg/g of stool or another unit appropriate for the analytical method. |
| Change in Fecal Secretory Immunoglobulin A Concentration | Baseline, 3 months, and 6 months | Fecal secretory immunoglobulin A (sIgA) will be measured as a marker of intestinal mucosal immune activity. Results will be reported as the concentration of secretory IgA in feces. |
| Change in Fecal Beta-Defensin Concentration | Baseline, 3 months, and 6 months | Selected beta-defensins will be measured in stool samples as markers of intestinal innate immune defense. Results will be reported as the concentration of individual beta-defensins in feces. |
| Change in Fecal Mucin Concentration | Baseline, 3 months, and 6 months | Fecal mucin concentration or selected mucin-associated markers will be measured to assess changes related to the intestinal mucus layer and mucosal protection. Results will be reported as the concentration of the analyzed mucin marker in feces. |
| Change in Total Fecal Short-Chain Fatty Acid Concentration | Baseline, 3 months, and 6 months | The total concentration of short-chain fatty acids (SCFAs) will be measured in stool samples as a marker of intestinal microbial fermentation activity. Results will be reported as the total concentration of SCFAs, for example in µmol/g or mg/g of stool. |
| Change in the Relative Proportions of Fecal Short-Chain Fatty Acids | Baseline, 3 months, and 6 months | The relative proportions of acetate, propionate, butyrate and other selected short-chain fatty acids will be determined. Results will be expressed as the percentage contribution of each SCFA to the total measured SCFA pool. |
| Change in Total Fecal Bile Acid Concentration | Baseline, 3 months, and 6 months | The total concentration of bile acids will be measured in stool samples to assess changes in intestinal bile acid metabolism. Results will be reported as the total concentration of measured bile acids in feces. |
| Change in Individual Fecal Bile Acid Concentrations | Baseline, 3 months, and 6 months | The concentrations of selected primary, secondary and conjugated bile acids will be measured in stool samples. Results will be reported separately for each identified bile acid. |
| Change in the Fecal Primary-to-Secondary Bile Acid Ratio | Baseline, 3 months, and 6 months | The ratio of primary to secondary bile acids in stool samples will be calculated from the concentrations of the identified bile acids. This measure will be used to assess changes in microbiota-associated bile acid transformation. |
| Change in Fecal Tryptophan Metabolite Concentrations | Baseline, 3 months, and 6 months | The concentrations of selected tryptophan metabolites will be measured in stool samples to assess changes in microbial and host-associated tryptophan metabolism. Results will be reported separately for each identified metabolite. |
| Change in Fecal Indole Metabolite Concentrations | Baseline, 3 months, and 6 months | The concentrations of indole and selected indole derivatives will be measured in stool samples. Analytes may include indole, indole-3-acetic acid, indole-3-lactic acid, indole-3-propionic acid and other selected metabolites, depending on the analytical method. |
| Change in Fecal Phenolic Acid Concentrations | Baseline, 3 months, and 6 months | The concentrations of selected phenolic acids and related microbial metabolites will be measured in stool samples. Results will be reported separately for each identified compound. |
| Change in Selected Markers of Intestinal Bacterial Metabolic Activity | Baseline, 3 months, and 6 months | Selected fecal metabolites reflecting intestinal bacterial activity will be measured in stool samples. The analysis may include metabolites derived from the microbial fermentation of carbohydrates, proteins, amino acids and dietary polyphenols. Results will be reported separately for each selected marker. |
| Change in Gut Microbiome Alpha Diversity | Baseline, 3 months, and 6 months | Gut microbiome alpha diversity will be assessed using molecular analysis of stool samples, such as 16S ribosomal RNA gene sequencing or shotgun metagenomic sequencing. Alpha-diversity indices may include the Shannon index, Simpson index, Chao1 index and the number of observed taxa. |
| Change in Gut Microbiome Beta Diversity | Baseline, 3 months, and 6 months | Gut microbiome beta diversity will be assessed using molecular analysis of stool samples, such as 16S ribosomal RNA gene sequencing or shotgun metagenomic sequencing. Differences in microbial community composition will be evaluated using appropriate distance measures, such as Bray-Curtis dissimilarity or UniFrac distance. |
| Change in the Relative Abundance of Selected Bacterial Taxa | Baseline, 3 months, and 6 months | The relative abundance of selected intestinal bacterial taxa will be determined using 16S ribosomal RNA gene sequencing or shotgun metagenomic sequencing. Results will be expressed as the percentage or proportion of sequencing reads assigned to individual taxa at the phylum, family, genus or species level, as permitted by the analytical method. |
| Change in Overall Gut Microbiome Composition | Baseline, 3 months, and 6 months | Overall gut microbiome composition will be evaluated using molecular analysis of stool samples. Changes in the distribution of bacterial taxa and the structure of the microbial community will be assessed between study time points and study groups. |
| Change in the Firmicutes-to-Bacteroidota Ratio | Baseline, 3 months, and 6 months | The ratio of the relative abundance of bacteria assigned to the phyla Firmicutes and Bacteroidota will be calculated from microbiome sequencing data. This parameter will be treated as an exploratory microbiome outcome. |
| Change in the Relative Abundance of Potentially Beneficial Bacterial Taxa | Baseline, 3 months, and 6 months | The relative abundance of selected bacterial taxa considered potentially beneficial to intestinal health, such as Bifidobacterium, Lactobacillus, Akkermansia and selected butyrate-producing bacteria, will be assessed. The final list of taxa will depend on the resolution and quality of the sequencing data. |
| Change in the Relative Abundance of Potentially Pro-Inflammatory or Opportunistic Bacterial Taxa | Baseline, 3 months, and 6 months | The relative abundance of selected potentially pro-inflammatory or opportunistic bacterial taxa will be assessed using microbiome sequencing data. The final list of taxa will be predefined in the statistical analysis plan or determined using an exploratory microbiome analysis. |
| Change in Gut Microbiome Functional Potential | Baseline, 3 months, and 6 months | When shotgun metagenomic sequencing is performed, the functional potential of the gut microbiome will be assessed based on the abundance of microbial genes, metabolic pathways or functional modules. Analyses may include pathways associated with short-chain fatty acid production, bile acid metabolism, tryptophan metabolism, intestinal barrier function and inflammatory processes. |
| Change in Plasma Asymmetric Dimethylarginine Concentration | Baseline, 3 months, and 6 months | Plasma asymmetric dimethylarginine (ADMA) concentration will be measured as an endogenous inhibitor of nitric oxide synthase and a marker associated with reduced nitric oxide bioavailability and endothelial dysfunction. Results will be reported as the concentration of ADMA in plasma. |
| Change in Plasma Symmetric Dimethylarginine Concentration | Baseline, 3 months, and 6 months | Plasma symmetric dimethylarginine (SDMA) concentration will be measured as a marker associated with methylarginine metabolism, renal function and impaired L-arginine transport. Results will be reported as the concentration of SDMA in plasma. |
| Change in Serum Adiponectin Concentration | Baseline, 3 months, and 6 months | Serum adiponectin concentration will be measured as an adipokine associated with insulin sensitivity, lipid metabolism and anti-inflammatory activity. |
| Change in the Integrated Lipid Metabolism Profile | Baseline, 3 months, and 6 months | An integrated lipid metabolism profile will be assessed using total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B100, apolipoprotein E and selected markers of lipid oxidation. |
| Change in Serum Creatine Kinase Activity | Baseline, 3 months, and 6 months | Serum creatine kinase activity will be measured as a marker of skeletal muscle cell injury and muscle membrane disruption. |
| Change in Serum Creatine Kinase-MB Activity or Concentration | Baseline, 3 months, and 6 months | Serum creatine kinase-MB activity or concentration will be measured as an exploratory marker of muscle injury, depending on the analytical method and study population. |
| Change in Blood Lactate Concentration | Baseline, 3 months, and 6 months | Blood lactate concentration will be measured as a marker of anaerobic metabolism and tissue metabolic activity. |
| Change in Plasma Free Glycerol Concentration | Baseline, 3 months, and 6 months | Plasma free glycerol concentration will be measured as a marker of adipose tissue lipolysis and triglyceride breakdown. |
| Change in Selected Markers of Skeletal Muscle Metabolism | Baseline, 3 months, and 6 months | Selected markers of skeletal muscle metabolism and injury will be measured in blood samples. The panel may include creatine kinase, creatine kinase isoenzymes, lactate and other predefined markers of muscle-cell metabolism. |
| Change in Selected Markers of Adipose Tissue Lipolysis | Baseline, 3 months, and 6 months | Selected circulating markers of adipose tissue lipolysis will be assessed, including free glycerol and other predefined metabolites associated with triglyceride breakdown. |
| Change in Circulating Free Fatty Acid Concentration | Baseline, 3 months, and 6 months | Serum or plasma non-esterified free fatty acid concentration will be measured as a marker of adipose tissue lipolysis and systemic lipid mobilization. |
| Change in the Integrated Adipose Tissue Metabolism Profile | Baseline, 3 months, and 6 months | An integrated exploratory profile of adipose tissue metabolism will be assessed using free glycerol, free fatty acids, adipokines and other predefined markers of adipocyte function. |
| Change in 8-Hydroxy-2'-Deoxyguanosine Concentration | Baseline, 3 months, and 6 months | The concentration of 8-hydroxy-2'-deoxyguanosine will be measured in serum, plasma or urine as a marker of oxidative DNA damage. |
| Change in Serum Uric Acid Concentration | Baseline, 3 months, and 6 months | Serum uric acid concentration will be measured as a marker of purine metabolism and as a compound associated with both antioxidant activity and cardiometabolic risk. |
| Change in Serum Osteocalcin Concentration | Baseline, 3 months, and 6 months | Serum osteocalcin concentration will be measured as a marker of osteoblast activity and bone formation. |
| Change in Serum Osteoprotegerin Concentration | Baseline, 3 months, and 6 months | Serum osteoprotegerin concentration will be measured as a regulatory marker of osteoclastogenesis and the receptor activator of nuclear factor kappa-B ligand pathway. |
| Change in Serum Dickkopf-Related Protein 1 Concentration | Baseline, 3 months, and 6 months | Serum Dickkopf-related protein 1 concentration will be measured as an inhibitor of Wnt signaling and a marker associated with bone formation regulation. |
| Change in Serum C-Terminal Telopeptide of Type I Collagen Concentration | Baseline, 3 months, and 6 months | Serum C-terminal telopeptide of type I collagen concentration will be measured as a marker of bone resorption. |
| Change in Serum Receptor Activator of Nuclear Factor Kappa-B Ligand Concentration | Baseline, 3 months, and 6 months | Serum receptor activator of nuclear factor kappa-B ligand concentration will be measured as a marker associated with osteoclast differentiation and bone resorption. |
| Change in Serum Receptor Activator of Nuclear Factor Kappa-B Concentration | Baseline, 3 months, and 6 months | Serum receptor activator of nuclear factor kappa-B concentration or expression will be assessed as a marker of signaling involved in osteoclast development and activation. |
| Change in the Receptor Activator of Nuclear Factor Kappa-B Ligand-to-Osteoprotegerin Ratio | Baseline, 3 months, and 6 months | The ratio of receptor activator of nuclear factor kappa-B ligand to osteoprotegerin will be calculated as an exploratory indicator of the balance between osteoclast activation and inhibition. |
| Change in Serum Procollagen Type I N-Terminal Propeptide Concentration | Baseline, 3 months, and 6 months | Serum procollagen type I N-terminal propeptide concentration will be measured as a marker of type I collagen synthesis and bone formation. |
| Change in Serum Bone-Specific Alkaline Phosphatase Activity | Baseline, 3 months, and 6 months | Serum bone-specific alkaline phosphatase activity or concentration will be measured as a marker of osteoblast activity and bone formation. |
| Change in Serum Tartrate-Resistant Acid Phosphatase 5b Concentration | Baseline, 3 months, and 6 months | Serum tartrate-resistant acid phosphatase 5b concentration or activity will be measured as a marker of osteoclast number and bone resorption. |
| Change in Urinary Deoxypyridinoline Concentration | Baseline, 3 months, and 6 months | Urinary deoxypyridinoline concentration will be measured as a marker of collagen degradation and bone resorption. Results may be normalized to urinary creatinine concentration. |
| Change in Serum Fibroblast Growth Factor 23 Concentration | Baseline, 3 months, and 6 months | Serum fibroblast growth factor 23 concentration will be measured as a regulator of phosphate and vitamin D metabolism. |
| Change in the Bone Formation Marker Profile | Baseline, 3 months, and 6 months | The bone formation marker profile will be assessed using osteocalcin, procollagen type I N-terminal propeptide, bone-specific alkaline phosphatase and other predefined markers of osteoblast activity. |
| Change in the Bone Resorption Marker Profile | Baseline, 3 months, and 6 months | The bone resorption marker profile will be assessed using C-terminal telopeptide of type I collagen, tartrate-resistant acid phosphatase 5b, urinary deoxypyridinoline and other predefined markers of osteoclast activity. |
| Change in the Integrated Bone Turnover Profile | Baseline, 3 months, and 6 months | An integrated exploratory bone turnover profile will be assessed using markers of bone formation, bone resorption and RANK-RANKL-osteoprotegerin signaling. |
| Change in the Integrated Adipokine Profile | Baseline, 3 months, and 6 months | An integrated exploratory adipokine profile will be assessed using selected markers of adipose tissue endocrine and inflammatory activity, including adiponectin, leptin, soluble leptin receptor, resistin, visfatin, omentin, chemerin, apelin, vaspin, retinol-binding protein 4, fatty acid-binding protein 4, tumor necrosis factor alpha, interleukin-6, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, lipocalin-2, progranulin, secreted frizzled-related protein 5, angiopoietin-like proteins 2 and 4, and asprosin. |
| Change in Circulating Caveolin-1 Concentration | Baseline, 3 months, and 6 months | Circulating caveolin-1 concentration will be measured as an exploratory marker associated with membrane signaling, lipid transport, endothelial function and metabolic regulation. |
| Change in Total Ghrelin Concentration | Baseline, 3 months, and 6 months | Total ghrelin concentration will be measured in plasma as a marker associated with appetite regulation, energy balance and glucose metabolism. |
| Change in Acylated Ghrelin Concentration | Baseline, 3 months, and 6 months | Acylated ghrelin concentration will be measured in appropriately stabilized plasma as the biologically active form of ghrelin. |
| Change in Des-Acyl Ghrelin Concentration | Baseline, 3 months, and 6 months | Des-acyl ghrelin concentration will be measured in plasma as the major circulating non-acylated form of ghrelin. |
| Change in the Acylated-to-Des-Acyl Ghrelin Ratio | Baseline, 3 months, and 6 months | The ratio of acylated ghrelin to des-acyl ghrelin will be calculated as an exploratory marker of ghrelin processing and biological activity. |
| Change in Circulating Integrin Concentration or Expression | Baseline, 3 months, and 6 months | The concentration or cellular expression of selected integrins will be assessed as markers of cell adhesion, extracellular matrix interactions, inflammation and vascular function. The specific integrin subunits will be predefined in the analytical protocol. |
| Change in Circulating Cadherin Concentration or Expression | Baseline, 3 months, and 6 months | The concentration or cellular expression of selected cadherins will be assessed as markers of intercellular adhesion and tissue barrier integrity. The specific cadherin type will be predefined in the analytical protocol. |
| Change in Soluble Vascular Endothelial Cadherin Concentration | Baseline, 3 months, and 6 months | Serum or plasma soluble vascular endothelial cadherin concentration will be measured as a marker associated with endothelial junction integrity and vascular permeability. |
| Change in E-Cadherin Concentration or Expression | Baseline, 3 months, and 6 months | E-cadherin concentration or cellular expression will be assessed as a marker of epithelial cell adhesion and tissue barrier integrity. |
| Change in Chemokine-Like Receptor 1 Expression | Baseline, 3 months, and 6 months | Chemokine-like receptor 1, also known as CMKLR1 or ChemR23, expression will be measured in the selected cell population as the principal functional receptor for chemerin. |
| Change in G Protein-Coupled Receptor 1 Expression | Baseline, 3 months, and 6 months | G protein-coupled receptor 1 expression will be measured in the selected biological material as a receptor involved in chemerin binding and signaling. |
| Change in C-C Chemokine Receptor-Like 2 Expression | Baseline, 3 months, and 6 months | C-C chemokine receptor-like 2 expression will be measured in the selected biological material as a non-classical chemerin-binding receptor involved in the regulation of local chemerin availability. |
| Change in the Chemerin Receptor Expression Profile | Baseline, 3 months, and 6 months | The expression profile of chemerin receptors will be assessed using CMKLR1, G protein-coupled receptor 1 and C-C chemokine receptor-like 2 in a predefined cell population or tissue-derived material. |
| Change in Glycated Hemoglobin | Baseline, 3 months, and 6 months | Glycated hemoglobin will be measured in whole blood as an indicator of average blood glucose concentration during the preceding approximately 2 to 3 months. Results will be reported as a percentage or in mmol/mol. |
| Change in Serum Glycated Albumin Concentration | Baseline, 3 months, and 6 months | Serum glycated albumin concentration or percentage will be measured as an indicator of average glycemic exposure during the preceding approximately 2 to 3 weeks. |
| Change in Plasma Methylglyoxal Concentration | Baseline, 3 months, and 6 months | Plasma methylglyoxal concentration will be measured as a reactive dicarbonyl compound associated with carbonyl stress and advanced glycation end-product formation. |
| Change in Plasma 3-Deoxyglucosone Concentration | Baseline, 3 months, and 6 months | Plasma 3-deoxyglucosone concentration will be measured as a reactive dicarbonyl intermediate involved in advanced glycation end-product formation. |
| Change in Carboxymethyllysine Concentration | Baseline, 3 months, and 6 months | Serum or plasma Nε-carboxymethyllysine concentration will be measured as a major advanced glycation end product associated with glycoxidative stress. |
| Change in Carboxyethyllysine Concentration | Baseline, 3 months, and 6 months | Serum or plasma Nε-carboxyethyllysine concentration will be measured as an advanced glycation end product associated with methylglyoxal exposure. |
| Change in Pentosidine Concentration | Baseline, 3 months, and 6 months | Serum, plasma or urinary pentosidine concentration will be measured as a fluorescent cross-linking advanced glycation end product. |
| Change in Methylglyoxal-Derived Hydroimidazolone 1 Concentration | Baseline, 3 months, and 6 months | Serum or plasma methylglyoxal-derived hydroimidazolone 1 concentration will be measured as a major methylglyoxal-derived advanced glycation end product. |
| Change in Soluble Receptor for Advanced Glycation End Products Concentration | Baseline, 3 months, and 6 months | Serum or plasma soluble receptor for advanced glycation end products concentration will be measured as a circulating decoy receptor associated with advanced glycation end-product signaling. |
| Change in Total Advanced Glycation End-Product Concentration | Baseline, 3 months, and 6 months | Total advanced glycation end-product concentration will be measured in serum or plasma using the predefined analytical method. |
| Change in Skin Autofluorescence | Baseline, 3 months, and 6 months | Skin autofluorescence may be measured non-invasively as an indirect marker of tissue accumulation of fluorescent advanced glycation end products. |
| Change in the Integrated Advanced Glycation End-Product Profile | Baseline, 3 months, and 6 months | An integrated exploratory advanced glycation end-product profile will be assessed using glycated hemoglobin, glycated albumin, methylglyoxal, 3-deoxyglucosone, carboxymethyllysine, carboxyethyllysine, pentosidine, methylglyoxal-derived hydroimidazolone 1, soluble receptor for advanced glycation end products and total advanced glycation end products. |
| Change in the Advanced Glycation End-Product-to-Soluble Receptor for Advanced Glycation End Products Ratio | Baseline, 3 months, and 6 months | The ratio of selected advanced glycation end products or total advanced glycation end products to soluble receptor for advanced glycation end products will be calculated as an exploratory indicator of the balance between glycation burden and circulating advanced glycation end-product-binding capacity. |
| Change in the Integrated Carbonyl Stress Profile | Baseline, 3 months, and 6 months | An integrated exploratory carbonyl stress profile will be assessed using protein carbonyls, methylglyoxal, 3-deoxyglucosone and selected advanced glycation end products. |
| Mean Change From Baseline in Serum Alpha-Crystallin B (CRYAB) Concentration | Baseline, 3 months, and 6 months | Serum alpha-crystallin B (CRYAB) concentration will be measured in stored serum samples using a quantitative enzyme-linked immunosorbent assay (ELISA). For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. Results will be reported in ng/mL. |
| Mean Change From Baseline in Serum Inorganic Phosphate Concentration | Baseline, 3 months, and 6 months | Serum inorganic phosphate concentration will be measured in stored serum samples using a validated clinical chemistry method. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Mean Change From Baseline in Serum Magnesium Concentration | Baseline, 3 months, and 6 months | Serum magnesium concentration will be measured in stored serum samples using a validated clinical chemistry method. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Serum Thyroid-Stimulating Hormone Concentration | Baseline, 3 months, and 6 months | Serum thyroid-stimulating hormone (TSH) concentration will be measured in stored serum samples using a validated immunoassay. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Serum Free Thyroxine Concentration | Baseline, 3 months, and 6 months | Serum free thyroxine (FT4) concentration will be measured in stored serum samples using a validated immunoassay. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Serum Free Triiodothyronine Concentration | Baseline, 3 months, and 6 months | Serum free triiodothyronine (FT3) concentration will be measured in stored serum samples using a validated immunoassay. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Serum Anti-Thyroid Peroxidase Antibody Concentration | Baseline, 3 months, and 6 months | Serum anti-thyroid peroxidase antibody (anti-TPO) concentration will be measured in stored serum samples using a validated immunoassay. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Serum Anti-Thyroglobulin Antibody Concentration | Baseline, 3 months, and 6 months | Serum anti-thyroglobulin antibody (anti-Tg) concentration will be measured in stored serum samples using a validated immunoassay. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Serum Vascular Endothelial Growth Factor A Concentration | Baseline, 3 months, and 6 months | Serum vascular endothelial growth factor A (VEGF-A) concentration will be measured in stored serum samples using a validated quantitative immunoassay. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group.Serum vascular endothelial growth factor A (VEGF-A) concentration will be measured in stored serum samples using a validated quantitative immunoassay. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Serum Vascular Endothelial Growth Factor C Concentration | Baseline, 3 months, and 6 months | Serum vascular endothelial growth factor C (VEGF-C) concentration will be measured in stored serum samples using a validated quantitative immunoassay. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Plasma Nitrate Concentration | Baseline, 3 months, and 6 months | Plasma nitrate concentration will be measured in stored plasma samples using a validated colorimetric, fluorometric or chromatographic method as a marker of nitric oxide metabolism. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Plasma Nitrite Concentration | Baseline, 3 months, and 6 months | Plasma nitrite concentration will be measured in stored plasma samples using a validated colorimetric, fluorometric or chromatographic method as a marker of nitric oxide metabolism. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Plasma Malondialdehyde Concentration | Baseline, 3 months, and 6 months | Plasma malondialdehyde (MDA) concentration will be measured in stored plasma samples using a validated chromatographic method as a marker of lipid peroxidation. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Malondialdehyde-Modified Low-Density Lipoprotein Concentration | Baseline, 3 months, and 6 months | Serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) will be measured in stored serum samples using a validated immunoassay as a marker of oxidative modification of low-density lipoproteins. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Fecal Acetate Concentration | Baseline, 3 months, and 6 months | Fecal \[acetate/propionate/butyrate/isobutyrate/valerate/isovalerate\] concentration will be quantified in stored stool samples using a validated gas chromatographic method. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Fecal Propionate Concentration | Baseline, 3 months, and 6 months | Fecal \[acetate/propionate/butyrate/isobutyrate/valerate/isovalerate\] concentration will be quantified in stored stool samples using a validated gas chromatographic method. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Fecal Butyrate Concentration | Baseline, 3 months, and 6 months | Fecal \[acetate/propionate/butyrate/isobutyrate/valerate/isovalerate\] concentration will be quantified in stored stool samples using a validated gas chromatographic method. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Fecal Isobutyrate Concentration | Baseline, 3 months, and 6 months | Fecal \[acetate/propionate/butyrate/isobutyrate/valerate/isovalerate\] concentration will be quantified in stored stool samples using a validated gas chromatographic method. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change From Baseline in Fecal Valerate Concentration | Baseline, 3 months, and 6 months | Fecal \[acetate/propionate/butyrate/isobutyrate/valerate/isovalerate\] concentration will be quantified in stored stool samples using a validated gas chromatographic method. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change in Plasma 6-Keto-Prostaglandin F1 Alpha Concentration | Baseline, 3 months, and 6 months | Plasma 6-keto-prostaglandin F1 alpha concentration will be measured as a stable metabolite of prostacyclin and an indirect marker of prostacyclin production. Results will be reported as the concentration of 6-keto-prostaglandin F1 alpha in plasma. |
| Change From Baseline in Fecal Isovalerate Concentration | Baseline, 3 months, and 6 months | Fecal \[acetate/propionate/butyrate/isobutyrate/valerate/isovalerate\] concentration will be quantified in stored stool samples using a validated gas chromatographic method. For each participant, changes from baseline at 3 and 6 months will be calculated and summarized as the mean change for each study group. |
| Change in Plasma Thromboxane B2 Concentration | Baseline, 3 months, and 6 months | Plasma thromboxane B2 (TXB2) concentration will be measured as a stable metabolite of thromboxane A2 and a marker associated with platelet activation and vasoconstrictive prostanoid activity. |
| Change in Plasma Prostaglandin F2 Alpha Concentration | Baseline, 3 months, and 6 months | Plasma prostaglandin F2 alpha (PGF2α) concentration will be measured as a marker of prostanoid pathway activity. Results will be reported as the concentration of PGF2α in plasma. |
| Change in Plasma Prostaglandin E2 Concentration | Baseline, 3 months, and 6 months | Plasma prostaglandin E2 (PGE2) concentration will be measured as a mediator associated with inflammation, vascular responses and immune regulation. |
| Change in Plasma Prostaglandin D2 Concentration | Baseline, 3 months, and 6 months | Plasma prostaglandin D2 (PGD2) concentration will be measured as a mediator involved in inflammatory, allergic and vascular processes. |
| Change in Plasma 13,14-Dihydro-Prostaglandin E1 Concentration | Baseline, 3 months, and 6 months | Plasma 13,14-dihydro-prostaglandin E1 concentration will be measured as a metabolite associated with prostaglandin E1 metabolism. Results will be reported as the concentration of the analyte in plasma. |
| Change in Plasma Leukotriene B4 Concentration | Baseline, 3 months, and 6 months | Plasma leukotriene B4 (LTB4) concentration will be measured as a pro-inflammatory lipid mediator associated with leukocyte recruitment and activation. |
| TRPV4 ion channel activity | Baseline, 3 months, and 6 months | TRPV4 ion channel activity is a measure of the level and functioning of a membrane protein responsible for detecting mechanical, osmotic, and thermal stimuli |
| Change in Plasma 15-Deoxy-Delta-12,14-Prostaglandin J2 Concentration | Baseline, 3 months, and 6 months | Plasma 15-deoxy-Δ12,14-prostaglandin J2 concentration will be measured as a cyclopentenone prostaglandin associated with the regulation and resolution of inflammatory responses. |
| Change in Plasma Dimethylamine Concentration | Baseline, 3 months, and 6 months | Plasma dimethylamine (DMA) concentration will be measured as a metabolite associated with the degradation of asymmetric dimethylarginine by dimethylarginine dimethylaminohydrolase. Results will be reported as the concentration of DMA in plasma. |
| Change in Plasma L-Arginine Concentration | Baseline, 3 months, and 6 months | Plasma L-arginine concentration will be measured as the principal substrate for nitric oxide synthase. Results will be reported as the concentration of L-arginine in plasma. |
| Change in Plasma Citrulline Concentration | Baseline, 3 months, and 6 months | Plasma citrulline concentration will be measured as a product of nitric oxide synthesis from L-arginine and as a marker associated with arginine-nitric oxide metabolism. Results will be reported as the concentration of citrulline in plasma. |
| Change in the L-Arginine-to-ADMA Ratio | Baseline, 3 months, and 6 months | The plasma L-arginine-to-ADMA ratio will be calculated as an exploratory indicator of nitric oxide synthase substrate availability relative to endogenous nitric oxide synthase inhibition. |
| Change in the ADMA-to-DMA Ratio | Baseline, 3 months, and 6 months | The plasma ADMA-to-DMA ratio will be calculated as an exploratory marker associated with ADMA metabolism and dimethylarginine dimethylaminohydrolase activity. |
| Change in Endothelial Nitric Oxide Synthase Concentration | Baseline, 3 months, and 6 months | Endothelial nitric oxide synthase (eNOS) concentration will be measured in stored serum samples using a quantitative enzyme-linked immunosorbent assay (ELISA). Change from baseline will be calculated separately at 3 and 6 months and summarized for each study group. Results will be expressed in ng/mL. |
| Change in Inducible Nitric Oxide Synthase Concentration | Baseline, 3 months, and 6 months | Inducible nitric oxide synthase (iNOS) concentration or activity will be measured as a marker associated with inflammation-related nitric oxide production. Results will be reported as iNOS concentration or enzymatic activity, depending on the analytical method. |
| Change in Dimethylarginine Dimethylaminohydrolase 1 Concentration | Baseline, 3 months, and 6 months | Dimethylarginine dimethylaminohydrolase 1 (DDAH1) concentration or activity will be measured as a marker of asymmetric dimethylarginine degradation and nitric oxide pathway regulation. |
| Change in Dimethylarginine Dimethylaminohydrolase 2 Concentration | Baseline, 3 months, and 6 months | Dimethylarginine dimethylaminohydrolase 2 (DDAH2) concentration or activity will be measured as a marker associated with asymmetric dimethylarginine metabolism and vascular nitric oxide regulation. |
| Change in Protein Arginine Methyltransferase 1 Concentration | Baseline, 3 months, and 6 months | Protein arginine methyltransferase 1 (PRMT1) concentration or activity will be measured as a marker associated with protein arginine methylation and the formation of methylated arginine derivatives, including ADMA. |
| Change in the Prostacyclin-to-Thromboxane Balance | Baseline, 3 months, and 6 months | The ratio of 6-keto-prostaglandin F1 alpha to thromboxane B2 will be calculated as an exploratory marker of the balance between prostacyclin-related vasodilatory activity and thromboxane-related platelet and vasoconstrictive activity. |
| Change in the Plasma Eicosanoid Profile | Baseline, 3 months, and 6 months | The plasma eicosanoid profile will be assessed based on concentrations of selected prostaglandins, prostanoids and leukotrienes, including 6-keto-prostaglandin F1 alpha, TXB2, PGF2α, PGE2, PGD2, 13,14-dihydro-PGE1, LTB4 and 15-deoxy-Δ12,14-PGJ2. |
| Change in Plasma Anandamide Concentration | Baseline, 3 months, and 6 months | Plasma anandamide, also known as arachidonoylethanolamide (AEA), concentration will be measured as an endogenous cannabinoid receptor ligand involved in the regulation of inflammation, metabolism, vascular function and pain signaling. |
| Change in Plasma 2-Arachidonoylglycerol Concentration | Baseline, 3 months, and 6 months | Plasma 2-arachidonoylglycerol (2-AG) concentration will be measured as a major endogenous cannabinoid receptor ligand involved in metabolic, immune and vascular regulation. |
| Change in Plasma 1-Arachidonoylglycerol Concentration | Baseline, 3 months, and 6 months | Plasma 1-arachidonoylglycerol (1-AG) concentration will be measured as an arachidonoylglycerol isomer associated with endocannabinoid metabolism. Results will be reported as the concentration of 1-AG in plasma. |
| Change in Plasma Palmitoylethanolamide Concentration | Baseline, 3 months, and 6 months | Plasma palmitoylethanolamide (PEA) concentration will be measured as an endocannabinoid-related lipid mediator associated with anti-inflammatory and analgesic pathways. |
| Change in Plasma Docosatetraenoylethanolamide Concentration | Baseline, 3 months, and 6 months | Plasma docosatetraenoylethanolamide (DEA) concentration will be measured as an N-acylethanolamine associated with endocannabinoid-related lipid signaling. Results will be reported as the concentration of DEA in plasma. |
| Change in the Plasma Endocannabinoid Profile | Baseline, 3 months, and 6 months | The plasma endocannabinoid and endocannabinoid-related lipid profile will be assessed based on concentrations of AEA, 2-AG, 1-AG, PEA and DEA. |
| Change in Serum High-Sensitivity C-Reactive Protein Concentration | Baseline, 3 months, and 6 months | Serum high-sensitivity C-reactive protein (hsCRP) concentration will be measured as a marker of low-grade systemic inflammation. Results will be reported as the concentration of hsCRP in serum. |
| Change in Serum Procalcitonin Concentration | Baseline, 3 months, and 6 months | Serum procalcitonin concentration will be measured as a marker associated with systemic inflammatory responses and bacterial infection-related inflammation. |
| Change in Serum Amyloid A Concentration | Baseline, 3 months, and 6 months | Serum amyloid A concentration will be measured as an acute-phase protein and a marker of systemic inflammatory activity. |
| Change in Serum Neopterin Concentration | Baseline, 3 months, and 6 months | Serum neopterin concentration will be measured as a marker of cellular immune activation, particularly activation of monocytes and macrophages. |
| Change in Serum Interleukin-10 Concentration | Baseline, 3 months, and 6 months | Serum interleukin-10 (IL-10) concentration will be measured as a marker of anti-inflammatory and immunoregulatory activity. |
| Change in Serum Interleukin-15 Concentration | Baseline, 3 months, and 6 months | Serum interleukin-15 (IL-15) concentration will be measured as a marker associated with immune-cell activation and inflammatory regulation. |
| Change in Serum Interleukin-1 Alpha Concentration | Baseline, 3 months, and 6 months | Serum interleukin-1 alpha (IL-1α) concentration will be measured as a marker of pro-inflammatory signaling and tissue-associated immune activation. |
Countries
Poland
Outcome results
None listed