Soluble Fibre Supplementation in NAFLD

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Non-Alcoholic Fatty Liver Disease, Non Alcoholic Steatohepatitis, Hepatic Steatosis

Intervention / Treatment
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* Dietary Supplement: Fructo-oligosaccharide enriched inulin supplement
* Other: Maltodextrin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible participants will be randomly allocated (1:1) to the OF+INU supplementation (intervention) or placebo group in a concealed fashion using REDCap databases, generated by a computer algorithm in permuted blocks of 2 and 4, to avoid imbalances. Study investigators and participants will be blinded to group allocation.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oligofructose Inulin Supplementation<br>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<br>* Experiment<br>|
| Sham Comparator: Maltodextrin Supplementation<br>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<br>* Placebo.<br>|

What is the study measuring?
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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 |