Soluble Fibre Supplementation in NAFLD (FIND)

The Efficacy of Soluble Fibre Supplementation for the Treatment of Pediatric Non-alcoholic Fatty Liver Disease (NAFLD)

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatic Steatosis; Non-Alcoholic Fatty Liver Disease; Non Alcoholic Steatohepatitis
• Intervention / Treatment: Other: Maltodextrin; Dietary supplement: Fructo-oligosaccharide enriched inulin supplement

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S4K1
      • Recruiting
      • McMaster University Medical Center
      • Contact: Paige Cheveldayoff, BSc; Phone Number: 306-361-1281; Email: cheveldp@mcmaster.ca
      • Contact: Nikhil Pai, MD; Phone Number: 73587 905.521.2100; Email: pain@mcmaster.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oligofructose Inulin Supplementation; 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.	Dietary supplement: Fructo-oligosaccharide enriched inulin supplement; Experiment
Sham Comparator: Maltodextrin Supplementation; 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).	Other: Maltodextrin; Placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hepatic fat content.	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.	Six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hepatic stiffness.	Hepatic stiffness, a measure of hepatic fibrosis, will be measured via MRI using standard techniques.	Six months
Change in glycemic control, or insulin resistance.	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).	Six months
Change in liver enzymes (ALT, AST, GGT, or ALP)	Liver enzymes will be measured using Abbott ARCHITECT Systems	Six months
Change in body fat percentage	Body fat will be measured using a DXA scanner, by research team members previously trained in DXA measurement.	Six months
Change in weight	Weight will be measured using an electronic platform scale.	Six months
Change in height	Height will be measured using a wall mounted stadiometer.	Six months
Change in BMI	BMI will be calculated mathematically from other outcomes such as height and weight.	Six months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in molecular profiling of gut microbiome	Profiling of the gut microbiome will be measured from collected stool samples	Six months

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR)

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2022
• Primary Completion (Anticipated): March 1, 2027
• Study Completion (Anticipated): March 1, 2027

Study Registration Dates

• First Submitted: July 22, 2022
• First Submitted That Met QC Criteria: July 27, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 14888; 471270 (Other Grant/Funding Number: CIHR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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