Soluble Fibre Supplement for Fatty Liver Disease
(FIND Trial)
Recruiting in Palo Alto (17 mi)
Overseen byNikhil Pai, MD
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: McMaster University
Must not be taking: Glucocorticoids, Antipsychotics, others
Disqualifiers: Diabetes, MRI contraindications, other liver disease, others
No Placebo Group
Prior Safety Data
Trial Summary
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.
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.
12345Is 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.
12567How 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.
14568Eligibility Criteria
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.
+1 more
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).
+4 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Oligofructose Inulin SupplementationExperimental Treatment1 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 SupplementationPlacebo Group1 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).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
McMaster University Medical CenterHamilton, Canada
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Who Is Running the Clinical Trial?
McMaster UniversityLead Sponsor
Canadian Institutes of Health Research (CIHR)Collaborator
References
Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial. [2022]Inulin-type fructans (ITF) are prebiotic dietary fibre (DF) that may confer beneficial health effects, by interacting with the gut microbiota. We have tested the hypothesis that a dietary intervention promoting inulin intake versus placebo influences fecal microbial-derived metabolites and markers related to gut integrity and inflammation in obese patients.
Inulin-Type β2-1 Fructans have Some Effect on the Antibody Response to Seasonal Influenza Vaccination in Healthy Middle-Aged Humans. [2022]β2-1 fructans are prebiotics and, as such, may modulate some aspects of immune function. Improved immune function could enhance the host's ability to respond to infections. There is limited information on the effects of β2-1 fructans on immune responses in humans. The objective of the study was to determine the effect of a specific combination of long-chain inulin and oligofructose (Orafti(®) Synergy1) on immune function in middle-aged humans, with the primary outcome being response to seasonal influenza vaccination. Healthy middle-aged humans (45-63 years of age) were randomly allocated to consume β2-1 fructans in the form of Orafti(®) Synergy1 (8 g/day; n = 22) or maltodextrin as control (8 g/day; n = 21) for 8 weeks. After 4 weeks, participants received the 2008/2009 seasonal influenza vaccine. Blood and saliva samples were collected prior to vaccination and 2 and 4 weeks after vaccination. They were used to measure various immune parameters. The primary outcome was the serum concentration of anti-vaccine antibodies. Serum antibody titers against the vaccine and vaccine-specific immunoglobulin concentrations increased post-vaccination. Antibodies to the H3N2-like hemagglutinin type 3, neuraminidase type 2-like strain were higher in the Synergy1 group (P = 0.020 for overall effect of treatment group), as was serum vaccine-specific IgG1 2 weeks post-vaccination (P = 0.028 versus control). There were no other differences between groups in antibody titers or anti-vaccine immunoglobulin concentrations, in blood immune cell phenotypes, or in a range of immune parameters. It is concluded that Orafti(®) Synergy1, a combination of β2-1 fructans, can enhance some aspects of the immune response in healthy middle-aged adults, but that this is not a global effect.
Inulin and oligofructose modulate lipid metabolism in animals: review of biochemical events and future prospects. [2017]Inulin and oligofructose, besides their effect on the gastro-intestinal tract, are also able to exert 'systemic' effect, namely by modifying the hepatic metabolism of lipids in several animal models. Feeding male Wistar rats on a carbohydrate-rich diet containing 10 % inulin or oligofructose significantly lowers serum triacylglycerol (TAG) and phospholipid concentrations. A lower hepatic lipogenesis, through a coordinate reduction of the activity and mRNA of lipogenic enzymes is a key event in the reduction of very low-density lipoprotein-TAG secretion by oligofructose. Oligofructose is also able to counteract triglyceride metabolism disorder occurring through dietary manipulation in animals, and sometimes independently on lipogenesis modulation: oligofructose reduces post-prandial triglyceridemia by 50 % and avoids the increase in serum free cholesterol level occurring in rats fed a Western-type high fat diet. Oligofructose protects rats against liver TAG accumulation (steatosis) induced by fructose, or occurring in obese Zucker fa/fa rats. The protective effect of dietary inulin and oligofructose on steatosis in animals, would be interesting, if confirmed in humans, since steatosis is one of the most frequent liver disorders, occurring together with the plurimetabolic syndrome, in overweight people. The panel of putative mediators of the systemic effects of inulin and oligofructose consists in either modifications in glucose/insulin homeostasis, the end-products of their colonic fermentation (i.e. propionate) reaching the liver by the portal vein, incretins and/or the availability of other nutrients. The identification of the key mediators of the systemic effects of inulin and oligofructose is the key to identify target function(s) (or dysfunction(s)), and finally individuals who would take an advantage of increasing their dietary intake.
Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study. [2015]In experimental animals, recent results suggest that the addition of inulin-type fructans such as oligofructose (OFS) in the diet decreases triacylglycerol accumulation in the liver tissue. Therefore, we have investigated the effect of daily ingestion of OFS in seven patients with nonalcoholic steatohepatitis (NASH), confirmed by liver biopsies.
Inulin and fructo-oligosaccharides have divergent effects on colitis and commensal microbiota in HLA-B27 transgenic rats. [2022]Modulation of intestinal microbiota by non-digestible carbohydrates may reduce inflammation in inflammatory bowel disease (IBD). The aim of the present study was to assess the effects of inulin and fructo-oligosaccharides (FOS) on intestinal microbiota and colitis in HLA-B27 transgenic rats, a well-validated rodent model for IBD. In this study, 4-week-old rats were fed 8 g/kg body weight inulin or FOS for 12 weeks, or not. Faeces were collected at 4 and 16 weeks of age; and caecal samples were collected at necropsy. The effects of inulin and FOS on chronic intestinal inflammation were assessed using a gross gut score, histology score and levels of mucosal IL-1β. Intestinal microbiota were characterised by quantitative PCR and denaturing gradient gel electrophoresis. Colitis was significantly reduced in all FOS-fed rats compared to the control diet, whereas inulin decreased chronic intestinal inflammation in only half the number of animals. Quantitative analysis of caecal microbiota demonstrated that inulin increased the numbers of total bacteria and the Bacteroides-Prevotella-Porphyromonas group, FOS increased bifidobacteria, and both fructans decreased Clostridium cluster XI. In the faecal samples, both inulin and FOS decreased total bacteria, Bacteroides-Prevotella-Porphyromonas group, and Clostridium clusters XI and XIVa. FOS increased Bifidobacterium spp., and mediated a decrease of gene copies of Enterobacteriaceae and Clostridium difficile toxin B in faeces. SCFA concentrations in the faecal and caecal samples were unaffected by the diets. In conclusion, FOS increased the abundance of Bifidobacterium spp., whereas both fructans reduced Clostridium cluster XI and C. difficile toxin gene expression, correlating with a reduction of chronic intestinal inflammation.
Friend or foe? The roles of inulin-type fructans. [2021]Inulin-type fructans (ITFs) as functional fructans and soluble dietary fiber are a mixture of inulin, oligofructose and fructooligosaccharide with β configuration. They are modified by gut microbiota at the end of ileum, subsequently, improve digestive system, metabolic syndrome, immune system and inflammatory diseases, and prevent against infection and cancer. However, it has been reported that inadequate consumption of ITFs aggravates the development of non-alcoholic fatty liver disease, results in gastrointestinal symptoms, liver cancer and intestinal inflammation. Therefore, this review summarizes the health benefits, pharmaceutical applications and safety evaluation of ITFs, which would direct their rational applications.
Inulin and oligofructose: safe intakes and legal status. [2018]Inulin and oligofructose are a significant part of the daily diet of most of the world's population. Daily intakes for the U.S. and Europe have been estimated at up to 10 g, specifically 1-4 g for the 97th percentile in the U.S. Because both inulin and oligofructose are macroingredients, it is difficult to apply classical toxicology tests. Although some high dose animal tests have been performed, none have revealed any toxic effects. The safety of inulin and oligofructose for use in foods was evaluated by many legal authorities worldwide. As a result, both inulin and oligofructose are accepted in most countries as food ingredients that can be used without restrictions in food formulations. In the U.S., a panel of experts performed a generally accepted as safe (GRAS) Self-Affirmation Evaluation in 1992 and concluded similarly. At high doses, increased flatulence and osmotic pressure can cause intestinal discomfort. These doses vary widely from person to person and also depend on the type of food in which inulin or oligofructose is incorporated. With regard to labeling, both inulin and oligofructose are gradually being accepted as "dietary fibers" in most countries around the world. The mention of their "bifidogenic effect" on food labels has also been legally accepted in several countries.
Randomised Double-Blind Placebo-Controlled Trial of Inulin with Metronidazole in Non-Alcoholic Fatty Liver Disease (NAFLD). [2021]Background: Non-alcoholic fatty liver disease (NAFLD) can be ameliorated by weight loss although difficult to maintain. Emerging evidence indicates that prebiotics and antibiotics improve NAFLD. Aim: To determine whether inulin supplementation after brief metronidazole therapy is effective in reducing alanine aminotransferase (ALT) and maintaining weight loss achieved through a very-low-calorie diet (VLCD) among people with NAFLD. Methods: Sixty-two people with NAFLD commenced 4-week VLCD using Optifast meal replacements (600 kcal/day). Sixty were then randomised into a 12-week double-blind, placebo-controlled, parallel three-arm trial: (1) 400 mg metronidazole twice daily in Week 1 then inulin 4 g twice daily OR (2) placebo twice daily in week one then inulin OR (3) placebo-placebo. Main outcomes were ALT and body weight at 12 weeks. Fecal microbiota changes were also evaluated. Results: Mean body mass index (BMI) and ALT reduced after VLCD by 2.4 kg/m2 and 11 U/L, respectively. ALT further decreased after metronidazole-inulin compared to after placebo-placebo (mean ALT change -19.6 vs. -0.2 U/L, respectively; p = 0.026); however, weight loss maintenance did not differ. VLCD treatment decreased the ratio of Firmicutes/Bacteroidetes (p = 0.002). Conclusion: Brief metronidazole followed by inulin supplementation can reduce ALT beyond that achieved after VLCD in patients with NAFLD.