Nonalcoholic Fatty Liver Disease, Nonalcoholic Fatty Liver Disease (NAFLD), MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD, NAFLD, Metabolic Dysfunction-Associated Steatotic Liver Disease, NAFLD (Nonalcoholic Fatty Liver Disease), NAFLD (Non-alcoholic Fatty Liver Disease), NAFLD - Non-Alcoholic Fatty Liver Disease, NAFLD - Nonalcoholic Fatty Liver Disease
Conditions
Keywords
LM pectin, pectin, MASLD, NAFLD, Nonalcoholic Fatty Liver Disease, Systemic Inflammatory Response, Dietary Fiber, Dietary Fibre, Diet, gut microbiota, Metabolic Dysfunction-Associated Steatotic Liver Disease
Brief summary
The goal of this clinical trial is to learn if daily supplementation with Low-methoxy (LM) pectin (polysaccharides extracted from citrus peels), which are commonly found in the UK diet (not pharmacological agents), can reduce systemic inflammation and improve gut microbiota composition in adults recently diagnosed with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The main question it aims to answer is: -How does dietary Low-methoxy (LM) pectin supplementation affect systematic inflammation pathways such as those mediated by gut microbiota composition and what are the impacts on general metabolic indicators in individuals with MASLD? Researchers will compare a group taking 15g of LM-pectin with 10g of cocoa powder to a placebo group receiving 10g of placebo with 10g of cocoa powder to see if LM-pectin has measurable effects on inflammation and gut microbiota. Participants will: * Take a daily supplement for 6 weeks: either 15g of LM-pectin with 10g of cocoa powder (intervention), or 10g of placebo with 10g of cocoa powder (control) * Provide stool and fasting blood samples before and after the intervention * Undergo anthropometric measurements (weight, height, waist/hip ratio, and blood pressure) * Complete a case report form (CRF) including demographics and health/medical history * Undergo a FibroScan™ to assess liver health * (Optional) Participate in MRI scans to evaluate gut permeability
Detailed description
Primary Objective: This research aims to study the effects of daily ingestion of LM pectin on inflammation pathways by measuring the blood inflammatory markers associated with physiological processes (TNFα, IL-6, IL-10, IFNᵞ, C - reactive protein, Zonulin (Haptoglobulin), IL-1β). Secondary Objectives: 1. Assessment of changes in anthropometric measures. 2. Assessment of changes in general metabolic indicators, such as fasting blood glucose and other blood-based markers relevant to MASLD (e.g., CK18-M30, CK18-M65, PROC3, Enhanced Liver Fibrosis (ELF), NIS2+™, YKL-40, microRNA miR-34a-5p, liver-associated enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), gamma-glutamyl transferase (GGT), Alkaline Phosphatase (ALP)), bilirubin levels, lipid profiles, and platelet counts. 3. Exploration of changes in gut microbiome composition. 4. Exploration of modifications in non-invasive physiological assessments linked to liver characteristics, such as fat content and stiffness through controlled attenuation parameter (CAP) and transient elastography. 5. Observation of alteration in fat in liver and other surrounding abdominal organs through Dixon MRI sequence in patients who will agree to have 2 MRI scans. 6. Validation of MRI measures (T2\*) as a tool to measure gut permeability among MASLD patients and investigation of changes in gut permeability in participants undergoing two MRI scans. 7. Investigation the presence of gene variants such as MUC2, encoding Mucin protein, that are associated with gut permeability.
Interventions
DIETARY_SUPPLEMENTPectin
15g of pectin with 10g of cocoa powder added as flavour were randomly allocated to eligible participants.
OTHERCocoa Powder
10g of cocoa powder served as the control/ placebo to compare the effects observed with pectin.
DIAGNOSTIC_TESTMagnetic Resonance Imaging with Contrast
To validate MRI scans as a tool to assess intestinal wall thickness to indicate gut permeability on MASLD patients, the investigators will scan 15 healthy volunteers twice, at baseline and after 6 weeks, and then compare their results with MASLD participant results at baseline and after 6 weeks.
Sponsors
Nottingham University Hospitals NHS Trust
University of Nottingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blinded.
Intervention model description
The study will be a parallel design, placebo-controlled, randomised dietary intervention study in which each participant will be randomly assigned to either pectin supplementation arm or control arm using online software (sealedenvelope.com).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for the main study: * Patients with clinical diagnosis of MASLD (formerly termed non-alcoholic fatty liver disease (NAFLD)), having assessment suggesting that liver fat \> 5% (e.g. histological evidence or/ and Transient Elastography using Controlled Attenuation Parameter (CAP)- FibroScan™ in the past month and/or liver imaging (such as ultrasound, computerized tomography (CT) or magnetic resonance imaging (MRI)). * Participants willing and able to give informed consent for participation in the study. * Participants aged ≥18 years who have a body mass index (BMI) between 18.5 and 39.9 kg/m2 and stable weight (weight gain or loss ≤ 3kg) for the past 3 months. * For diabetic participants: controlled blood glucose levels Haemoglobin A1C (HbA1c) \<7.0% (\<53 mmol/mol) \[1\]. * Able to undergo CAP-FibroScan™. Inclusion criteria for healthy participants who will have MRI scans: * Participants willing and able to give informed consent for participation in the study. * Participants aged ≥18 years. * participants with CAP\<250 kpa\<8kP by a FibroScan™ within the past 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of blood markers contributing to systemic inflammation pathway (TNFα (pg/mL), IL-6 (pg/mL), IL-10 (pg/mL), IFNᵞ (pg/mL), C-Reactive Protein (pg/mL), Zonulin (Haptoglobulin)(pg/m), IL-1β(pg/mL)). | 6 weeks | Change in circulating markers of inflammation measured by ELISAs in serum samples collected pre and post the 6-weeks intervention period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of changes in general metabolic indicators, such as fasting blood glucose and other blood-based markers relevant to MASLD (e.g., CK18-M30, CK18-M65, PROC3, Enhanced Liver Fibrosis (ELF), NIS2+™, YKL-40, microRNA miR-34a-5p) | 6 weeks | Changes in general metabolic indicators, such as fasting blood glucose and other blood-based markers relevant to MASLD (e.g., CK18-M30, CK18-M65, PROC3, Enhanced Liver Fibrosis (ELF), NIS2+™, YKL-40, microRNA miR-34a-5p) pre and post the 6-weeks intervention period. |
| Assessment of changes in liver-associated enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), gamma-glutamyl transferase (GGT), Alkaline Phosphatase (ALP)), bilirubin levels, lipid profiles, and platelet counts. | 6 weeks | Changes in liver-associated enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), gamma-glutamyl transferase (GGT), Alkaline Phosphatase (ALP)), bilirubin levels, lipid profiles, and platelet counts pre and post the 6-weeks intervention period. |
| Change in Liver Stiffness via Transient Elastography | 6 weeks | CAP and liver stiffness (in kPa) measured using transient elastography. |
| Change in Liver Fat Fraction Assessed by Dixon MRI Sequence. | 6 weeks | Fat fraction (%) in liver and abdominal organs assessed using Dixon MRI before and after the 6-week intervention. |
| Change in Intestinal Permeability Measured by T2* MRI. | 6 weeks | T2\* values in gut wall tissue will be compared before and after the intervention as a proxy for gut permeability. |
| Change in BMI (kg/m²) | 6 weeks | Changes in BMI pre and post the 6-weeks intervention period. |
| Change in Systolic Blood Pressure (mmHg) | 6 weeks | Change in Systolic Blood Pressure (mmHg) before and after the 6-week intervention. |
| Change in Diastolic Blood Pressure (mmHg) | 6 weeks | Change in Diastolic Blood Pressure (mmHg) before and after the 6-week intervention. |
| Change in Heart Rate (beats/minute) | 6 weeks | Change in Heart Rate (beats/minute) before and after the 6-week intervention. |
| Change in Waist-to-Hip Ratio | 6 weeks | Change in Waist-to-Hip Ratio before and after the 6-week intervention. |
| Investigation the presence of gene variants such as MUC2, encoding Mucin protein, that are associated with gut permeability. | 6 weeks | Genetic variants such as MUC2 will be determined where consent for genetic analysis is given. |
Countries
United Kingdom
Contacts
Primary ContactNoor K Al-Tameemi, PhD student candidate
Backup ContactGuruprasad P Aithal, Professor
Outcome results
None listed