Prebiotic Fibre Supplementation and Gut Microbiota in Non-alcoholic Fatty Liver Disease

Study Overview
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Brief Summary
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Non-alcoholic fatty liver disease (NAFLD) is a condition where accumulation of fat in the liver leads to metabolic dysfunction. Currently there are no approved treatments for NAFLD. Part of the metabolic dysfunction may arise through changes in the gut microbiota. Prebiotic fibres have beneficial effects on glucose tolerance, body weight, and gut microbiota; therefore they may have potential as part of a dietary strategy for NAFLD treatment.

Detailed Description
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The main objective of this study is to assess the effect of prebiotic fibre supplementation, in conjunction with diet-induced weight loss, on reduction in liver fat and injury. Primary Objective - determine the change in hepatic injury (fibrosis and inflammation) and hepatic fat (percent fat) over 6 months in NAFLD patients treated with prebiotic or placebo during weight loss. Secondary Objectives - determine the changes in appetite, body composition, glycemic and insulinemic responses, quality of life with prebiotic or placebo during weight loss, and examine mechanisms related to prebiotic-induced changes in gut microbiota and lipogenesis.

Official Title
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Prebiotic Fibre Supplementation and Gut Microbiota in Non-alcoholic Fatty Liver Disease

Conditions
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Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Dietary Supplement: Prebiotic fibre
* Dietary Supplement: Placebo
* Behavioral: Weight Loss


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects diagnosed with NAFLD on the basis of abnormal liver enzymes (ALT>1.5x upper limit of normal) and ultrasonography Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease Aspartate aminotransferase and alanine aminotransferase ≤10x upper limit of normal Patients with type 2 diabetes treated with diet and exercise alone or metformin Exclusion Criteria: Cirrhosis of the liver (FibroScan >17.5 kilopascal or FibroTest >0.8) or clinical features of cirrhosis. Alcohol consumption >20g/day (2 standard drinks) in women or > 30g/d (3 drinks) in men Alternate (e.g. TPN) or concomitant etiology for abnormal liver enzymes. History of decompensated liver disease including ascites, encephalopathy or variceal bleeding Concomitant use of any weight loss medication, previous bariatric or other intestinal surgery Presence of active infection, pregnancy or lactation Regular use of a probiotic or prebiotic supplement within 3 months prior to enrollment Antibiotic use within 3 months prior to enrollment Weight loss >3 kg within preceding 3 months to enrollment Uncontrolled cardiovascular or respiratory disease, active malignancy, or chronic infections Use of agents such as vitamin E, omega-3 fatty acids or medications with evidence for effects on NAFLD (pioglitazone, Glucagon-like peptide-1 analogues, dipeptidyl peptidase IV inhibitors, ursodeoxycholic acid) Patients with type 2 diabetes where HbA1c is >9%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prebiotic Fibre<br>The intervention group will receive two 8g packets/day of prebiotic fibre to add to 250 ml of water and consume 30 minutes prior to breakfast and dinner. | Dietary Supplement: Prebiotic fibre<br>* Oligofructose-enriched inulin (Synergy1)<br>Behavioral: Weight Loss<br>* All participants will receive 10 one-on-one sessions with a Registered Dietitian designed to achieve 10% weight loss over 6 months. The sessions will focus on nutrition education and behavior counseling to reduce food intake and improve dietary quality.<br>|
| Placebo Comparator: Placebo<br>The control group will receive two 3g packets/day of maltodextrin to add to 250 ml of water and consume 30 minutes prior to breakfast and dinner. | Dietary Supplement: Placebo<br>* Maltodextrin<br>Behavioral: Weight Loss<br>* All participants will receive 10 one-on-one sessions with a Registered Dietitian designed to achieve 10% weight loss over 6 months. The sessions will focus on nutrition education and behavior counseling to reduce food intake and improve dietary quality.<br>|
| Other: Weight Loss<br>All participants will be supported through Registered Dietitian visits to achieve approximately 10% weight loss. | Behavioral: Weight Loss<br>* All participants will receive 10 one-on-one sessions with a Registered Dietitian designed to achieve 10% weight loss over 6 months. The sessions will focus on nutrition education and behavior counseling to reduce food intake and improve dietary quality.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Liver Fat | Assessed via MRI | 24 weeks | 
| Change in Liver Fibrosis | Assessed via FibroScan (transient elastography) | 24 weeks | 
| Change in Liver Injury | Assessed via Fibrotest Score (composite score from serum biochemical markers: alfa2-macroglobulin, apolipoproteinA1, total bilirubin, haptoglobin, gamma glutamyl transpeptidase, alanine aminotransferase) | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glucose Tolerance | Assessed via an oral glucose tolerance test | 24 weeks | 
| Change in Glycemic Control | Assessed via HbA1c | 24 weeks | 
| Change in Subjective Appetite | Assessed via Subjective appetite ratings on a visual analogue scale | 24 weeks | 
| Change in Satiety Hormones | Assessed in serum as pg/ml (Ghrelin, Glucagon-like peptide-1, Glucose-dependent insulinotropic polypeptide, leptin and Peptide tyrosine tyrosine) | 24 weeks | 
| Change in Body Composition | Assessed via dual x-ray absorptiometry | 24 weeks | 
| Change in Quality of Life | Assessed via the Short Form-36v2 Health Survey questionnaire | 24 weeks | 
| Dietary Adherence | Assessed via adherence to prescribed versus measured energy intake assessed by food records | 24 weeks | 
| Examine mechanisms related to prebiotic-induced changes in gut microbiota, their metabolic byproducts, and de novo lipogenesis | Via investigating gut microbiota shot-gun sequencing and measurement of volatile organic compounds and de novo lipogenesis using deuterium incorporation | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dietary intervention, Prebiotic fibre, Weight loss, Gut microbiota, Obesity, Liver fat, Hepatic fibrosis