Histological Improvement of NASH With Prebiotic

Study Overview
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Brief Summary
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This trial will investigate the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. In a single-blind, placebo controlled, randomized pilot trial will be conduced in individuals with liver biopsy confirmed NASH (Non-alcoholic fatty liver activity score (NAS) ≥ 5). Participants will be randomized to receive oligofructose (8 g/day for 12 weeks and 16g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure is the change in liver biopsy NAS score and the secondary outcomes include changes in body weight, body composition, glucose tolerance, serum lipids, inflammatory markers, and gut microbiota.

Detailed Description
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Oligofructose and maltodextrin are both white powders that taste and look the same. They were both package in individual foil packets. Participants were blinded to the treatment allocation. Adherence to supplement protocol was monitored throughout the study through direct questioning and counting unused supplement packages. Participants were asked to maintain their usual physical activity.

Official Title
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Histological Improvement of Non-alcoholic Steatohepatitis With a Prebiotic: a Pilot Clinical Trial

Conditions
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Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Dietary Supplement: Prebiotic oligofructose
* Dietary Supplement: Placebo maltodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver biopsy confirmed NASH (NAS score greater than or equal to 5) BMI >25 kg/m2 (Caucasians) >23 kg/m2 (Asians) History of Serum ALT >1.5X upper normal limit No changes in lipid-lowering or diabetes medication over previous three months Ability to provide informed consent Exclusion Criteria: alcohol consumption >20g/day (women) or >30g/day (men) alternate etiology for abnormal liver enzymes decompensated liver disease use of orlistat, liraglutide, prebiotic, probiotic, or antibiotic within 3 months prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Interventional Model Description: Single-blind, placebo controlled, randomized trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prebiotic<br>Prebiotic oligofructose (Orafti P95, Beneo-Orafti Inc., Tienen, Belgium) taken 8g orally per day for 12 weeks followed by 16g per day for 24 weeks. | Dietary Supplement: Prebiotic oligofructose<br>* Powder format<br>|
| Placebo Comparator: Placebo<br>Placebo maltodextrin (isocaloric to prebiotic) taken 3.3g orally per day for 12 weeks followed by 6.6g per day for 24 weeks. | Dietary Supplement: Placebo maltodextrin<br>* Powder format<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological change | Nonalcoholic fatty liver disease activity score | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | Body lean and fat mass | 9 months | 
| Body weight | Body weight measurement | 9 months | 
| Glucose tolerance | Oral glucose tolerance test | 9 months | 
| Gut microbiota | Intestinal microbiota composition | 9 months | 
| Serum total cholesterol | Total cholesterol | 9 months | 
| Serum LDL cholesterol | Low-density lipoprotein cholesterol | 9 months | 
| Serum triglycerides | Triglycerides | 9 months | 
| Serum HDL cholesterol | High-density lipoprotein cholesterol | 9 months | 
| Serum IL-6 | Interleukin-6 | 9 months | 
| Serum TNF-alpha | Tumor necrosis factor - alpha | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gut microbiota, Prebiotic, Liver biopsy, Oligofructose