Clinical trial NCT02568605: Prebiotic Fibre Supplementation and Gut Microbiota in Non-alcoholic Fatty Liver Disease
Official title: Prebiotic Fibre Supplementation and Gut Microbiota in Non-alcoholic Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease
Keywords: Dietary intervention
Prebiotic fibre
Weight loss
Gut microbiota
Obesity
Liver fat
Hepatic fibrosis
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2015-10-06
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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%

Primary outcomes:
measure: Change in Liver Fat
timeFrame: 24 weeks
measure: Change in Liver Fibrosis
timeFrame: 24 weeks
measure: Change in Liver Injury
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in Glucose Tolerance
timeFrame: 24 weeks
measure: Change in Glycemic Control
timeFrame: 24 weeks
measure: Change in Subjective Appetite
timeFrame: 24 weeks
measure: Change in Satiety Hormones
timeFrame: 24 weeks
measure: Change in Body Composition
timeFrame: 24 weeks
measure: Change in Quality of Life
timeFrame: 24 weeks
measure: Dietary Adherence
timeFrame: 24 weeks
measure: Examine mechanisms related to prebiotic-induced changes in gut microbiota, their metabolic byproducts, and de novo lipogenesis
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Raylene A Reimer, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.