Fiber Supplementation and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance: Interactions With the Gut Microbiome.
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- University of Alberta
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- Changes in HOMA-IR
Study Overview
Brief Summary
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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Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Masking Description
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.
Eligibility Criteria
- Ages
- 12 Years to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 12-18 years
- •BMI percentile > 95% for age/sex;
- •Total weight fluctuation over past 6 months < 10%;
- •HOMA-IR > 3.16;
- •FH of T2DM (first or second-degree relative).
Exclusion Criteria
- •Current use of insulin or diagnosis of T2DM;
- •Systolic or diastolic blood pressure (BP) > 99th percentile for age and sex;
- •Acute infectious or inflammatory condition over the preceding 1 month; hospitalization > 48 hrs;
- •History of chronic disease such as inflammatory bowel disease, chronic severe liver or kidney disease or neurologic disorders;
- •Active malignancy;
- •Concomitant use of medication/investigational drug known to affect body weight in the past year;
- •Antibiotic use in past 60 days; probiotic and/or prebiotic supplements use in the past 30 days; use of lipid-lowering and anti-inflammatory medication.
Arms & Interventions
MET
MET (850 mg po bid - standard of care) + Fiber placebo daily
Intervention: Metformin 850 mg oral tablet bid (Drug)
FIBER
Fiber supplementation [35g fiber daily] + MET placebo po bid
Intervention: Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX. (Dietary Supplement)
FIBER + MET
Fiber supplementation [35g fiber daily] + MET 850 mg po bid
Intervention: Metformin 850 mg oral tablet bid (Drug)
FIBER + MET
Fiber supplementation [35g fiber daily] + MET 850 mg po bid
Intervention: Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX. (Dietary Supplement)
Outcomes
Primary Outcomes
Changes in HOMA-IR
Time Frame: Baseline, 6, and 12 months
Change in HOMA-IR value
Secondary Outcomes
- Changes in perceived hunger and satiety(Baseline, 6, and 12 months)
- Changes in gut microbiota composition(Baseline, 6, and 12 months)
- Changes in gut microbiome functions(Baseline, 6, and 12 months)
- Changes in body weight(Baseline, 6, and 12 months)
- Changes in body mass index (BMI)(Baseline, 6, and 12 months)
- Changes in body composition(Baseline, 6, and 12 months)
- Changes in inflammation(Baseline, 6, and 12 months)
- Changes in metabolic function(Baseline, 6, and 12 months)
- Changes in satiety hormones(Baseline, 6, and 12 months)
- Changes in quality of life(Baseline, 6, and 12 months)
- Changes in intestinal barrier integrity(Baseline, 6, and 12 months)