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

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.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Prebiotic fibre; Behavioral: Weight Loss; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • University of Calgary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prebiotic Fibre; 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; Oligofructose-enriched inulin (Synergy1); Behavioral: Weight Loss; 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.
Placebo Comparator: Placebo; 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.	Behavioral: Weight Loss; 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.; Dietary supplement: Placebo; Maltodextrin
Other: Weight Loss; All participants will be supported through Registered Dietitian visits to achieve approximately 10% weight loss.	Behavioral: Weight Loss; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Raylene A Reimer, PhD, RD, University of Calgary

Publications and helpful links

General Publications

• Lambert JE, Parnell JA, Eksteen B, Raman M, Bomhof MR, Rioux KP, Madsen KL, Reimer RA. Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol. BMC Gastroenterol. 2015 Dec 3;15:169. doi: 10.1186/s12876-015-0400-5.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): August 1, 2022

Study Registration Dates

• First Submitted: September 30, 2015
• First Submitted That Met QC Criteria: October 2, 2015
• First Posted (Estimate): October 6, 2015

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Obesity; Hepatic fibrosis; Weight loss; Gut microbiota; Liver fat; Dietary intervention; Prebiotic fibre
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: UC-REB14-2464

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided