Histological Improvement of NASH With Prebiotic

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Prebiotic oligofructose; Dietary supplement: Placebo maltodextrin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Prebiotic; 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; Powder format
PLACEBO_COMPARATOR: Placebo; 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; Powder format

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Raylene A Reimer, PhD, RD, The University Of Calgary

Publications and helpful links

General Publications

• Bomhof MR, Parnell JA, Ramay HR, Crotty P, Rioux KP, Probert CS, Jayakumar S, Raman M, Reimer RA. Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial. Eur J Nutr. 2019 Jun;58(4):1735-1745. doi: 10.1007/s00394-018-1721-2. Epub 2018 May 19.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 28, 2012
• Primary Completion (ACTUAL): December 16, 2015
• Study Completion (ACTUAL): May 30, 2016

Study Registration Dates

• First Submitted: June 8, 2017
• First Submitted That Met QC Criteria: June 9, 2017
• First Posted (ACTUAL): June 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 12, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Prebiotic; Gut microbiota; Liver biopsy; Oligofructose
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: E-23936

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Other researchers would need to make an individual inquiry.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No