Clinical trial NCT04578652: Fiber and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance
Official title: Fiber Supplementation and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance: Interactions With the Gut Microbiome.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Obesity, Childhood
Insulin Resistance
Keywords: Dietary fiber
Metformin
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2020-10-08
Enrollment: 90
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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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Eligibility criteria: Inclusion Criteria:

1. Age 12-18 years
2. BMI percentile \> 95% for age/sex;
3. Total weight fluctuation over past 6 months \< 10%;
4. HOMA-IR \> 3.16;
5. FH of T2DM (first or second-degree relative).

Exclusion Criteria:

1. Current use of insulin or diagnosis of T2DM;
2. Systolic or diastolic blood pressure (BP) \> 99th percentile for age and sex;
3. Acute infectious or inflammatory condition over the preceding 1 month; hospitalization \> 48 hrs;
4. History of chronic disease such as inflammatory bowel disease, chronic severe liver or kidney disease or neurologic disorders;
5. Active malignancy;
6. Concomitant use of medication/investigational drug known to affect body weight in the past year;
7. 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.

Primary outcomes:
measure: Changes in HOMA-IR
timeFrame: Baseline, 6, and 12 months
Secondary outcomes:
measure: Changes in body weight
timeFrame: Baseline, 6, and 12 months
measure: Changes in body mass index (BMI)
timeFrame: Baseline, 6, and 12 months
measure: Changes in body composition
timeFrame: Baseline, 6, and 12 months
measure: Changes in inflammation
timeFrame: Baseline, 6, and 12 months
measure: Changes in metabolic function
timeFrame: Baseline, 6, and 12 months
measure: Changes in satiety hormones
timeFrame: Baseline, 6, and 12 months
measure: Changes in quality of life
timeFrame: Baseline, 6, and 12 months
measure: Changes in perceived hunger and satiety
timeFrame: Baseline, 6, and 12 months
measure: Changes in gut microbiota composition
timeFrame: Baseline, 6, and 12 months
measure: Changes in gut microbiome functions
timeFrame: Baseline, 6, and 12 months
measure: Changes in intestinal barrier integrity
timeFrame: Baseline, 6, and 12 months
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: University of Alberta
name: Andrea M Haqq, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.