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?

This trial tests the effects of a fiber supplement on children with non-alcoholic fatty liver disease (NAFLD), a condition where fat accumulates in the liver without alcohol use. Participants receive either a fructo-oligosaccharide enriched inulin supplement (a type of soluble fiber) or a placebo to determine its effectiveness in reducing liver fat. Children enrolled in a specific nutrition clinic, who have obesity and show signs of NAFLD, are suitable candidates. The trial includes dietary analysis, blood tests, and special MRI scans to measure liver fat. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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 there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that inulin and fructo-oligosaccharides, components of the soluble fiber supplement under study, are generally safe for consumption. These ingredients commonly appear in foods and supplements. Studies have found that high amounts of fructo-oligosaccharides over time reduced weight and liver fat in mice. Although conducted on animals, this research suggests some level of safety for humans.

Inulin supports gut health by promoting the growth of beneficial bacteria, which can aid individuals with non-alcoholic fatty liver disease (NAFLD). The widespread use of these ingredients further supports their safety. However, consulting a healthcare provider before starting any new treatment is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fatty liver disease?

Unlike the standard treatments for fatty liver disease that often focus on lifestyle changes like diet and exercise or medications targeting liver enzymes, the fructo-oligosaccharide enriched inulin supplement introduces a novel approach by leveraging the power of soluble fiber. This supplement is unique because it works by enhancing the gut microbiome, which can play a significant role in reducing liver fat and inflammation. Researchers are particularly excited about this treatment because it is a simple, natural dietary addition that can easily be incorporated into daily routines, offering a potentially effective and low-risk alternative to current therapies.

What evidence suggests that this treatment might be an effective treatment for fatty liver disease?

This trial will compare a fructo-oligosaccharide enriched inulin supplement with a maltodextrin placebo. Research has shown that fructo-oligosaccharides, like those in the supplement under study, might help reduce liver fat. In animal studies, these supplements positively affected gut bacteria, potentially lowering fat build-up in the liver. Some studies observed improvements in liver health due to these changes. While more research is needed, these early findings suggest the supplement could help children with non-alcoholic fatty liver disease. ^{1 3 4 6 7}

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 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 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 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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05480696?cond=%22Fatty%20Liver%22&aggFilters=status:not%20rec&rank=3

NCT05480696 | Soluble Fibre Supplementation in 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 ...

2. withpower.com withpower.com/trial/phase-1-liver-diseases-8-2022-73054

Soluble Fibre Supplement for Fatty Liver Disease (FIND Trial) Research suggests that inulin and oligofructose, components of the treatment, can reduce liver fat accumulation in animal models, which is promising for ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7613160/

Investigation of synbiotic treatment in non-alcoholic fatty ... Synbiotic treatment was effective in changing gut microbiota but this pro- and prebiotic combination was ineffective in improving liver fat content or liver ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223000884

Fructooligosaccharides attenuate non-alcoholic fatty liver ... FOSs alleviated the pathological phenotype of NAFLD via remodeling of the gut microbiota composition and decreasing hepatic lipid metabolism.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05480696

NCT05480696 | Soluble Fibre Supplementation in 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 ...

6. mdpi.com mdpi.com/2813-0464/3/1/8

Fructooligosaccharides Supplementation: A Good Choice ... Long-term supplementation with high doses of FOS was effective in reducing weight, adiposity, NAFLD and serum cholesterol in C57BL mice with obesity and MS.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10449545/

Immunomodulatory effects of inulin and its intestinal ... A reduced abundance of F. prausnitzii has been observed in patients with nonalcoholic fatty liver disease (NAFLD). Inulin can provide carbon ...