Soluble Fibre Supplementation in NAFLD

Phase 2

Recruiting

• Conditions: Non-Alcoholic Fatty Liver Disease; Hepatic Steatosis; Non Alcoholic Steatohepatitis
• Interventions: Other: Maltodextrin; Dietary Supplement: Fructo-oligosaccharide enriched inulin supplement

• Registration Number: NCT05480696
• Lead Sponsor: McMaster University

Brief Summary

The FIND study will look at the effect of a nutritional mixed fibre supplement, oligofructose and inulin (OF+INU), on children with non-alcoholic fatty liver disease. In this randomized, double- blind controlled trial, subjects will be given a supplement, in the form of oral pills, and will have bloodwork performed, their diets analyzed, and liver fat measured at several timepoints. Liver fat will be measured by using a specialized MRI device located at St. Joseph's Hospital. Subjects will be recruited from the Children's Exercise and Nutrition Clinic.

Detailed Description

The FIND (Fibre in Non-Alcoholic Fatty Liver Disease) study will be a single-centre, randomized, double-blind placebo-controlled trial comparing the effects of 6 months of mixed oligofructose and inulin (OF+INU) supplementation vs placebo on hepatic fat content, hepatic stiffness, metabolic outcomes, and body composition in children ages 8-17 years old.

Assessments such as MRI measurements of hepatic fat and hepatic stiffness, anthropometry and pubertal status questionnaires, and other investigations such as body composition via dual energy X-ray absorptiometry (DXA), fasting lipids, liver enzymes, blood glucose and oral-glucose tolerance (OGTT) tests will be performed; and randomization will be conducted via REDCap software.

Eighty participants will be enrolled for baseline evaluation in order to randomize sixty participants for the intervention phase (i.e. thirty participants per study group). Participants will consume one packet (4g) of OF+INU or placebo (Maltodextrin) daily. If tolerated, this will increase to one packet twice daily. Several strategies will be implemented to increase compliance, including text message reminders (daily for first week, then weekly), study calls to assess compliance and tolerability, and check-ins with participants at each clinic visit. These interactions will allow the study team to assess challenges and offer prompt support. Compliance will be assessed at each study visit by counting empty and unused sachets. Treatment with OF+INU or placebo will occur for 6 months, with study visits being conducted at baseline evaluation, 3 months and 6 months

Study Timeline

• Study First Submitted: 2022-07-22
• Study First Submitted QC: 2022-07-27
• Study First Posted: 2022-07-29
• Study Start: 2022-09-09
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-08
• Last Update Posted: 2024-11-11
• Primary Completion: 2027-03
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Children ages 8-17 years
• Diagnosed with obesity (BMI ≥2 standard deviations above WHO reference median)
• Enrolled in GHWM Clinic
• Clinical evidence of NAFLD (elevation of ALT, greater than 2x upper-limit-of-normal (ULN) [ALT>80 IU/L for 8-17 years of age], and hepatic steatosis measured as part of clinic enrolment).

Exclusion Criteria

• Type 1, Type 2 diabetes mellitus (T1DM, T2DM)
• Contraindications to having MRI (claustrophobia, metal implant, recent tattoo, weight > 300lbs)
• Concomitant use of other fibre supplements
• Medications known to affect hepatic fat content, taken within the past year (i.e., glucocorticoids, anabolic steroids, tetracycline, anticonvulsants, antipsychotics, glucose- lowering medications)
• Presence of another known cause of liver disease
• Known allergy or hypersensitivity to OF-INU supplementation
• Self-reported alcohol intake >7 drinks/week or 3 drinks/day

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Maltodextrin Supplementation	Maltodextrin	The control group will receive a daily supplementation of carbohydrate placebo (isocaloric maltodextrin), identical in colour, packaging, preparation, and dose (4g, twice daily; C\*Dry MD™,Cargill).
Oligofructose Inulin Supplementation	Fructo-oligosaccharide enriched inulin supplement	The intervention group will receive a daily fibre supplementation of (fructo-oligosaccharide enriched inulin, 4g twice daily; Orafti®Synergy1, BENEO), a tasteless white powder contained within a tear-able, partitioned 4g sachet, sprinkled and dissolved in 125 mL of water.

Primary Outcome Measures

Name	Time	Method
Change in hepatic fat content.	Six months	Hepatic fat content will be measured via MRI at baseline and 6-months using standard techniques, optimized for accuracy, precision and reproducibility of proton density fat fraction (PDFF) quantification.

Secondary Outcome Measures

Name	Time	Method
Change in hepatic stiffness.	Six months	Hepatic stiffness, a measure of hepatic fibrosis, will be measured via MRI using standard techniques.
Change in weight	Six months	Weight will be measured using an electronic platform scale.
Change in body fat percentage	Six months	Body fat will be measured using a DXA scanner, by research team members previously trained in DXA measurement.
Change in height	Six months	Height will be measured using a wall mounted stadiometer.
Change in liver enzymes (ALT, AST, GGT, or ALP)	Six months	Liver enzymes will be measured using Abbott ARCHITECT Systems
Change in glycemic control, or insulin resistance.	Six months	Measured using plasma glucose (fasting and + 2 hours following oral glucose load) and HbA1c from a 2-hour OGTT (1.75g/kg, up to maximum of 75g glucose administered).
Change in BMI	Six months	BMI will be calculated mathematically from other outcomes such as height and weight.

Trial Locations

Locations (1)

McMaster University Medical Center; 🇨🇦 Hamilton, Ontario, Canada