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

Non-alcoholic Fatty Liver Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02568605
• Other study ID #: UC-REB14-2464
• Status: Completed
• Phase: N/A
• Start date: May 2015
• Est. completion date: August 2022

Study information

• Verified date: October 2022
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: August 2022
• Est. primary completion date: August 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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%

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

Dietary Supplement:
• Prebiotic fibre
Oligofructose-enriched inulin (Synergy1)
• Placebo
Maltodextrin

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.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta

Sponsors (2)

Lead Sponsor	Collaborator
University of Calgary	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Liver Fat	Assessed via MRI	24 weeks
Primary	Change in Liver Fibrosis	Assessed via FibroScan (transient elastography)	24 weeks
Primary	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	Change in Glucose Tolerance	Assessed via an oral glucose tolerance test	24 weeks
Secondary	Change in Glycemic Control	Assessed via HbA1c	24 weeks
Secondary	Change in Subjective Appetite	Assessed via Subjective appetite ratings on a visual analogue scale	24 weeks
Secondary	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
Secondary	Change in Body Composition	Assessed via dual x-ray absorptiometry	24 weeks
Secondary	Change in Quality of Life	Assessed via the Short Form-36v2 Health Survey questionnaire	24 weeks
Secondary	Dietary Adherence	Assessed via adherence to prescribed versus measured energy intake assessed by food records	24 weeks
Secondary	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