Hypertension, Obesity
Conditions
Brief summary
Cardiovascular risk factors such as obesity, diabetes, high blood pressure, high cholesterol, or smoking are associated with an increased risk of events such as myocardial infarction, stroke, or peripheral artery disease. Lifestyle and dietary measures, as well as pharmacological treatments, can help correct these risk factors. However, several studies have shown that even with optimal treatment, individuals at high risk still face a residual cardiovascular risk. This phenomenon is primarily attributed to the development of vascular lesions, meaning damage within the blood vessels. These lesions are largely due to inflammation, an activated immune state that is more pronounced in overweight individuals and significantly contributes to vascular damage, potentially shortening the lifespan of those with cardiovascular disease. Although anti-inflammatory therapies have proven effective in reducing this risk, they may interfere with tissue repair and the immune system. For this reason, it is essential to identify strategies that promote the resolution of inflammation without compromising these vital processes. Specialized pro-resolving mediators (SPMs) are compounds derived from omega-3 and omega-6 polyunsaturated fatty acids, which are naturally found in various foods such as fish. These mediators help limit the infiltration of inflammatory cells and initiate the repair of damaged tissues. This type of dietary supplement is already available over the counter, but its health benefits have not been extensively studied. Experimental animal studies have shown that restoring inflammation resolution through SPMs can prevent-or even reverse-cardiovascular damage and inflammation by directly acting on vascular cells and modulating the immune system. However, human data on the role of SPMs and inflammation resolution in vascular disease remain very limited. The investigators hypothesize that in individuals at high cardiovascular risk (due to obesity and hypertension), increasing circulating levels of SPMs through oral supplementation (as a dietary supplement) would improve vascular function, metabolic profile, and inflammatory and immune cell responses. In doing so, this may help reduce the residual risk of cardiovascular disease. The objective of this research is to assess whether a supplement enriched with SPMs can facilitate the resolution of inflammation, which is essential for restoring vascular function and thereby supporting the body's natural tissue repair mechanisms. To address the research question, the study plans to include 60 individuals with obesity and hypertension, all presenting a high cardiovascular risk, recruited from healthcare facilities located in France. This research is publicly funded by the French National Research Agency (Agence Nationale de la Recherche) through the European research project RESPIN-VAR, co-funded by ERA4Health and the European Union.
Interventions
DIETARY_SUPPLEMENTOral SPM-enriched marine oil (LIPINOVA)
LIPINOVA is an oral dietary supplement provided by Solutex, consisting of marine oil enriched in specialized pro-resolving mediator (SPM) precursors. Each daily dose (3 g/day) includes 1500 mg of omega-3 free fatty acids and a minimum of 520 mcg of SPM precursors (17-HDHA, 18-HEPE, 14-HDHA). The supplement is administered orally in 6 softgel capsules per day (3 after breakfast, 3 after dinner) over 12 weeks. It is used to investigate its effect on vascular function and inflammation in patients with obesity-related hypertension. The product is over-the-counter and commonly available in the EU, including France.
DIETARY_SUPPLEMENTPlacebo
Placebo capsules provided by Solutex, identical in appearance to LIPINOVA, contain refined olive oil with no active omega-3 fatty acids or SPM precursors. The placebo is administered orally in 6 softgel capsules per day (3 after breakfast, 3 after dinner) for 12 weeks, following a randomized, double-blind, crossover design. It serves as a control to evaluate the effects of SPM-enriched marine oil on vascular and inflammatory parameters in patients with obesity-related hypertension.
Sponsors
Assistance Publique - Hôpitaux de Paris
National Research Agency, France
The Company SOLUTEXGC, S.L
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 and 85 years,. * Hypertension controlled under pharmacological or non-pharmacological treatment, defined as office BP\< 140/90 mmHg at the Inclusion visit, * BMI \> 30 kg/m², * Stable antihypertensive treatment one month before inclusion (V1), * Signed informed consent, * Social security affiliation.
Exclusion criteria
* Secondary hypertension on the basis of medical history, * History of stroke in the previous 6 months on the basis of medical history, * Myocardial infarction in the previous 6 months on the basis of medical history, * Severe hepatic insufficiency on the basis of medical history, * Chronic kidney disease (DFG \< 30 ml/min 1.73 according to MDRD method), * Pregnancy or breast feeding, * Regular treatment with NO-donors or phosphodiesterase inhibitors, * Inability to comply with protocol requirements, * Patient under tutorship or / guardianship or/ safeguard of justice, and incapable to give informed consent, * Patient on AME (state medical aid), * Participation in another interventional study involving human participants , * Allergy to the ultrasound gel, * Hypersensitivity , allergy, or idiosyncratic reaction to omega-3 acids, fish or soya allergies. * Chronic inflammatory diseases, on the basis of medical history, * Chronic anti-inflammatory treatment administered within the past month preceding the Inclusion visit, * Any supplementation with omega-3 or omega-6 polyunsaturated fatty acids within the past month, * Life expectancy less than one year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow-mediated dilation (FMD) | FMD will be measured at Week 0 (baseline), Week 12 (after a first administration period of 12 weeks ± 2 days) , Week 16 (after a wash-out period of 2 weeks ± 2 days), Week 28 (after a second administration period of 12 weeks ± 2 days) | Conduit-artery endothelial function measured by flow-mediated dilation (FMD) after 12 week-intervention with oral SPM supplementation or placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Shear rate area under the curve (SR-AUC) | These parameters will be measured at Week 0 (baseline), Week 12 (after a first administration period of 12 weeks ± 2 days) , Week 16 (after a wash-out period of 2 weeks ± 2 days), Week 28 (after a second administration period of 12 weeks ± 2 days) | SR-AUC measured as the integral of brachial artery shear rate (flow velocity/diameter\*0,8) following post-ischemic reactive hyperemia induced by 5-min forearm cuff occlusion during FMD test |
| Difference after 12 -week- intervention with oral SPM supplementation or placebo in arterial stiffness | These parameters will be measured at Week 0 (baseline), Week 12 (after a first administration period of 12 weeks ± 2 days) , Week 16 (after a wash-out period of 2 weeks ± 2 days), Week 28 (after a second administration period of 12 weeks ± 2 days) | Arterial stiffness measured by cfPWV, office brachial and central BP and central hemodynamics measured by Sphygmocor CVMS. |
| Change from initiation to the end of the 12 -week- intervention in endothelial injury | These parameters will be measured at Week 0 (baseline), Week 12, Week 16, Week 28. | This outcome assesses endothelial injury by measuring a panel of biological markers that together reflect vascular endothelial function and inflammatory status. The selecting markers includes: panel of 15 markers including sICAM, sVCAM, eSelectin, vWF, based on ELISA (in house assay), electrochemiluminescence (V-PLEX, MesoScale Discoveries) and LuminexTM technologies.) and inflammatory cytokines (16 different cytokines including CRP, SAA, IL-6, IL-8, TNF-a) |
| Change from initiation to the end of the 12 -week- intervention immune cell profile | These parameters will be measured at Week 0, Week12, Week16, Week28 | A panel of 12 soluble immune checkpoints as potential novel actors in cardiovascular disease will be quantified including sCD25 (IL-2Ra), s4-1BB, sCD27, sCD86 (B7.2), TGF-β1 (free active form), sCTLA-4, and sGalectin-9, among others. PBMCs will be assayed for their activation capabilities by means of multiparametric intracellular spectral flow cytometry in the presence of a polyclonal stimulation. |
| Insulin sensitivity | These parameters will be measured at Week 0, Week12, Week16, Week28 | Insulin sensitivity will be assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), calculated from fasting glucose and insulin levels. This outcome evaluates metabolic response to the intervention. |
| Change in Body Fat Mass | These parameters will be measured at Week 0, Week12, Week16, Week28 | Body fat mass will be measured using a validated smart scale based on bioelectrical impedance. This outcome assesses changes in body composition during the intervention period. |
| Change in Lipid profile | These parameters will be measured at Week 0, Week12, Week16, Week28 | Serum total cholesterol, HDL cholesterol, and triglycerides concentration will be measured as a marker of lipid metabolism. |
| Safety assessement by Liver function markers | These parameters will be measured at Week 0, Week12, Week16, Week28 | Description : Liver function markers are AST, ALT, gammaGT |
| Safety assessement by Renal function markers | These parameters will be measured at Week 0, Week12, Week16, Week28 | Renal function will be evaluated through a composite of serum creatinine, serum uric acid, and urinalysis parameters (albuminuria/creatinuria ratio). |
| Safety assessement by Coagulation markers | These parameters will be measured at Week 0, Week12, Week16, Week28 | Coagulation function will be evaluated through a composite of prothrombin time and activated partial thromboplastin time. |
| SPM levels | These parameters will be measured at Week 0, Week12, Week16, Week28 | SPM levels |
| Questionnaires about perceptions and expectations about oral supplements for cardiovascular disease prevention | Week 0 and Week 28 | Change in Perceptions and Expectations Regarding Oral Supplements for Cardiovascular Disease Prevention Participants will complete a questionnaire assessing their perceptions and expectations about the use of oral supplements forcardiovascular disease prevention. |
| Health Literacy Questionnaire | Week 28 | Participants health literacy will be evaluated at the end of the intervention using a validated health literacy questionnaire. The objective is to assess their ability to access, understand, and use health-related information for decision-making. |
| Questionnaire about vascular ageing awareness | Week 28 | Questionnaire about vascular ageing awareness |
Countries
France
Contacts
CONTACTTiffany MARTIN
PRINCIPAL_INVESTIGATORRosa Maria BRUNO
Assistance Publique - Hôpitaux de Paris
Outcome results
None listed