Soluble Fibre Supplement for Fatty Liver Disease

(FIND Trial)

Overseen By Paige AL Cheveldayoff, BSC

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: McMaster University

Must not be taking: Glucocorticoids, Antipsychotics, others

Disqualifiers: Diabetes, MRI contraindications, other liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 6 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications known to affect liver fat content, such as glucocorticoids, anabolic steroids, tetracycline, anticonvulsants, antipsychotics, and glucose-lowering medications, if you've taken them in the past year.

Is the soluble fiber supplement safe for humans?

Inulin and fructo-oligosaccharides, which are part of the soluble fiber supplement, are generally considered safe for human consumption and are widely used in foods. They are recognized as safe by many legal authorities, although high doses can cause intestinal discomfort like gas. ^{1 2 3 4 5}

How does the treatment with Fructo-oligosaccharide enriched inulin differ from other treatments for fatty liver disease?

This treatment is unique because it uses prebiotic fibers like inulin and fructo-oligosaccharides to improve gut health, which may help reduce liver fat and inflammation. Unlike other treatments that might focus on weight loss or medication, this approach targets the gut microbiota to potentially improve liver health. ^{2 3 5 6 7}

What data supports the effectiveness of the treatment Fructo-oligosaccharide enriched inulin supplement for fatty liver disease?

Research suggests that inulin and oligofructose, components of the treatment, can reduce liver fat accumulation in animal models, which is promising for conditions like fatty liver disease. Additionally, these components have shown potential in improving lipid metabolism and reducing inflammation, which could be beneficial for liver health. ^{1 2 5 6 8}

Who Is on the Research Team?

Nikhil Pai, MD

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

This trial is for children aged 8-17 with obesity and non-alcoholic fatty liver disease (NAFLD), evidenced by elevated ALT levels and hepatic steatosis. They must be enrolled in the GHWM Clinic without diabetes, other liver diseases, or contraindications to MRI. Those using other fibre supplements or with allergies to OF-INU supplementation are excluded.

Inclusion Criteria

Enrolled in GHWM Clinic

I am between 8 and 17 years old.

My BMI is significantly higher than the average.

Exclusion Criteria

Contraindications to having MRI (claustrophobia, metal implant, recent tattoo, weight > 300lbs)

Concomitant use of other fibre supplements

I have diabetes (Type 1 or Type 2).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Evaluation

Baseline evaluation including MRI measurements, anthropometry, and questionnaires

1 week

1 visit (in-person)

Treatment

Participants receive daily supplementation of OF+INU or placebo for 6 months

6 months

3 visits (in-person at baseline, 3 months, and 6 months)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fructo-oligosaccharide enriched inulin supplement
• Fructo-oligosaccharide supplement

Trial Overview The FIND study tests if a mixed fibre supplement (oligofructose + inulin) can improve liver health in kids with NAFLD. Participants will randomly receive either this supplement or a placebo (Maltodextrin), have their diet analyzed, bloodwork done, and liver fat measured via MRI at St. Joseph's Hospital.

How Is the Trial Designed?

Group I: Oligofructose Inulin Supplementation Experimental Treatment 1 Intervention

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.

Group II: Maltodextrin Supplementation Placebo Group 1 Intervention

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).

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

In a 3-month randomized, placebo-controlled trial involving 24 obese patients, the intake of inulin-type fructans (ITF) significantly increased levels of beneficial gut bacteria, specifically Bifidobacterium, and reduced fecal calprotectin, a marker of gut inflammation.

The study suggests that ITF may help improve gut health in obese individuals by decreasing inflammation and potentially influencing gut microbiota-derived metabolites, although it did not significantly change short-chain fatty acid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial. Neyrinck, AM., Rodriguez, J., Zhang, Z., et al.[2022]

In a study involving 43 healthy middle-aged adults, the prebiotic Orafti(®) Synergy1, which contains β2-1 fructans, significantly enhanced the immune response to the seasonal influenza vaccine, particularly increasing antibody levels against specific viral components.

While Orafti(®) Synergy1 improved certain immune parameters, it did not affect all aspects of immune function, indicating that its benefits may be specific rather than universal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inulin-Type β2-1 Fructans have Some Effect on the Antibody Response to Seasonal Influenza Vaccination in Healthy Middle-Aged Humans. Lomax, AR., Cheung, LV., Noakes, PS., et al.[2022]

In a study with male Wistar rats, a diet containing 10% inulin or oligofructose significantly reduced serum triacylglycerol and phospholipid levels, indicating a potential for these fibers to improve lipid metabolism.

Oligofructose not only lowered triglyceride levels after meals by 50% but also protected against liver fat accumulation, suggesting it could be beneficial for preventing liver disorders like steatosis, especially in overweight individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inulin and oligofructose modulate lipid metabolism in animals: review of biochemical events and future prospects. Delzenne, NM., Daubioul, C., Neyrinck, A., et al.[2017]

In a pilot study involving 7 patients with nonalcoholic steatohepatitis (NASH), daily ingestion of 16 g of oligofructose (OFS) for 8 weeks significantly reduced liver enzymes, indicating potential liver health benefits.

While OFS improved liver function markers like aspartate aminotransferase and insulin levels, it did not significantly affect plasma lipid levels, suggesting its mechanism may be more focused on liver function rather than lipid metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study. Daubioul, CA., Horsmans, Y., Lambert, P., et al.[2015]

In a study involving HLA-B27 transgenic rats, feeding fructo-oligosaccharides (FOS) significantly reduced chronic intestinal inflammation compared to a control diet, while inulin was effective in only half of the rats.

Both inulin and FOS altered the intestinal microbiota by increasing beneficial bacteria like Bifidobacterium spp. and decreasing harmful bacteria such as Clostridium, which correlated with reduced inflammation in the gut.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inulin and fructo-oligosaccharides have divergent effects on colitis and commensal microbiota in HLA-B27 transgenic rats. Koleva, PT., Valcheva, RS., Sun, X., et al.[2022]

Inulin-type fructans (ITFs) are beneficial for health as they improve digestion, support the immune system, and may help prevent metabolic syndrome, infections, and cancer, highlighting their potential as a functional dietary fiber.

Inadequate intake of ITFs can lead to serious health issues, including non-alcoholic fatty liver disease and gastrointestinal problems, emphasizing the importance of sufficient consumption for maintaining overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Friend or foe? The roles of inulin-type fructans. Man, S., Liu, T., Yao, Y., et al.[2021]

Inulin and oligofructose are widely considered safe food ingredients, with no toxic effects found in high-dose animal tests, and they are accepted for unrestricted use in food formulations by legal authorities globally.

While daily intakes are generally safe, high doses can lead to intestinal discomfort, such as increased flatulence, which varies among individuals and depends on the food type, highlighting the importance of moderation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inulin and oligofructose: safe intakes and legal status. Coussement, PA.[2018]

In a study of 62 participants with non-alcoholic fatty liver disease (NAFLD), a very-low-calorie diet (VLCD) led to significant reductions in both body weight and alanine aminotransferase (ALT) levels, indicating improved liver health.

Following a brief course of metronidazole, inulin supplementation further decreased ALT levels compared to a placebo, suggesting that this combination may enhance liver function in NAFLD patients, although it did not significantly help maintain weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised Double-Blind Placebo-Controlled Trial of Inulin with Metronidazole in Non-Alcoholic Fatty Liver Disease (NAFLD). Chong, CYL., Orr, D., Plank, LD., et al.[2021]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Inulin-Type β2-1 Fructans have Some Effect on the Antibody Response to Seasonal Influenza Vaccination in Healthy Middle-Aged Humans. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Inulin and oligofructose modulate lipid metabolism in animals: review of biochemical events and future prospects. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Inulin and fructo-oligosaccharides have divergent effects on colitis and commensal microbiota in HLA-B27 transgenic rats. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Friend or foe? The roles of inulin-type fructans. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Inulin and oligofructose: safe intakes and legal status. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Randomised Double-Blind Placebo-Controlled Trial of Inulin with Metronidazole in Non-Alcoholic Fatty Liver Disease (NAFLD). [2021]