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This is a 12-month, single center, three-arm parallel design, double-blind, randomized clinical trial, to compare the effects of supplemental dietary fiber and metformin (MET) alone and in combination over 12 months on glucose metabolism (insulin resistance [IR]), inflammation and BMI in adolescents with obesity and IR, and to assess the relationship between therapeutic intervention(s) and changes in gut microbiome composition and function.
Since MET and FIBER have been shown to reduce weight and increase insulin sensitivity through distinct but overlapping mechanisms of action, our central hypothesis is that the combination of FIBER + MET will have a synergistic effect and be more effective than FIBER or MET alone in improving metabolic function (IR) and reducing BMI and inflammation in adolescents with obesity, IR and family history (FM) of T2DM.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MET | Active Comparator | MET (850 mg po bid - standard of care) + Fiber placebo daily |
|
| FIBER | Active Comparator | Fiber supplementation [35g fiber daily] + MET placebo po bid |
|
| FIBER + MET | Experimental | Fiber supplementation [35g fiber daily] + MET 850 mg po bid |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin 850 mg oral tablet bid | Drug | MET dose: 500 mg daily, increasing to 500 bid if tolerated after 2 weeks, then increasing again 2 weeks later to 850 mg bid (1700 mg daily). |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in HOMA-IR | Change in HOMA-IR value | Baseline, 6, and 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in body weight | Body weight measured in kg | Baseline, 6, and 12 months |
| Changes in body mass index (BMI) | BMI percentile and z-score according to age and sex will be estimated |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Andrea M Haqq, MD, MHS | Contact | 780-492-0015 | haqq@ualberta.ca |
| Name | Affiliation | Role |
|---|---|---|
| Andrea M Haqq, MD, MHS | University of Alberta | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alberta | Recruiting | Edmonton | Alberta | T6G 2E1 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40637175 | Derived | Fahim SM, Huey SL, Palma Molina XE, Agarwal N, Ridwan P, Ji N, Kibbee M, Kuriyan R, Finkelstein JL, Mehta S. Gut microbiome-based interventions for the management of obesity in children and adolescents aged up to 19 years. Cochrane Database Syst Rev. 2025 Jul 10;7(7):CD015875. doi: 10.1002/14651858.CD015875. | |
| 33596993 | Derived |
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Participants and research team will be blinded to the type of intervention allocated to each arm until the end of the study. Concealment will be protected by secure, password protected website. The group not on MET (fiber alone) will receive a placebo pill. The group not on fiber will also receive a placebo, composed of the same base solution without added fibers.
| Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX. | Dietary Supplement | The first week of treatment will use 1/3 the daily treatment dose; then 2/3 dose for the second and third weeks; then the full dose thereafter, to allow time for adaptation. |
|
| Baseline, 6, and 12 months |
| Changes in body composition | Body density using air-displacement plethysmography will be assessed to estimate fat mass and fat-free mass. | Baseline, 6, and 12 months |
| Changes in inflammation | Markers of inflammation that will be measured are: high-sensitivity C-reactive protein, interleukin, tumor necrosis factor-alpha) | Baseline, 6, and 12 months |
| Changes in metabolic function | The markers of metabolic function that will be measured are: fasting glucose, lipids (total, high and low density lipoprotein cholesterol; triglycerides), and oral glucose tolerance test. | Baseline, 6, and 12 months |
| Changes in satiety hormones | Markers of satiety that will be measured are: acylated ghrelin, peptide tyrosine tyrosine, GLP-1, leptin, and adiponectin. | Baseline, 6, and 12 months |
| Changes in quality of life | Quality of life will be measured by the a questionnaire | Baseline, 6, and 12 months |
| Changes in perceived hunger and satiety | Perceived hunger and satiety will be assessed by a questionnaire | Baseline, 6, and 12 months |
| Changes in gut microbiota composition | Fecal microbiota composition will be characterized by 16S rRNA gene amplicons sequencing using taxonomic and non-taxonomic based approaches. | Baseline, 6, and 12 months |
| Changes in gut microbiome functions | Fecal microbiome functions will be assessed through whole metagenomic sequencing, stool SCFAs and bile acids, and plasma metabolomics. | Baseline, 6, and 12 months |
| Changes in intestinal barrier integrity | Plasma lipopolysaccharide-binding protein and fecal calprotectin will be determined as measures of gut barrier integrity | Baseline, 6, and 12 months |
| Deehan EC, Colin-Ramirez E, Triador L, Madsen KL, Prado CM, Field CJ, Ball GDC, Tan Q, Orsso C, Dinu I, Pakseresht M, Rubin D, Sharma AM, Tun H, Walter J, Newgard CB, Freemark M, Wine E, Haqq AM. Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial. Trials. 2021 Feb 17;22(1):148. doi: 10.1186/s13063-021-05060-8. |
| ID | Term |
|---|---|
| D063766 | Pediatric Obesity |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| C120489 | oligofructose |
| D006170 | Gum Arabic |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D053149 | Plant Gums |
| D001704 | Biopolymers |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D053147 | Plant Exudates |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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