Insulin Resistance, Obesity, Childhood
Conditions
Keywords
Dietary fiber, Metformin
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. .
Interventions
DRUGMetformin 850 mg oral tablet bid
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).
DIETARY_SUPPLEMENTSupplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.
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.
Sponsors
University of Alberta
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, 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
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in HOMA-IR | Baseline, 6, and 12 months | Change in HOMA-IR value |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in body mass index (BMI) | Baseline, 6, and 12 months | BMI percentile and z-score according to age and sex will be estimated |
| Changes in body composition | Baseline, 6, and 12 months | Body density using air-displacement plethysmography will be assessed to estimate fat mass and fat-free mass. |
| Changes in inflammation | Baseline, 6, and 12 months | Markers of inflammation that will be measured are: high-sensitivity C-reactive protein, interleukin, tumor necrosis factor-alpha) |
| Changes in metabolic function | Baseline, 6, and 12 months | 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. |
| Changes in satiety hormones | Baseline, 6, and 12 months | Markers of satiety that will be measured are: acylated ghrelin, peptide tyrosine tyrosine, GLP-1, leptin, and adiponectin. |
| Changes in body weight | Baseline, 6, and 12 months | Body weight measured in kg |
| Changes in perceived hunger and satiety | Baseline, 6, and 12 months | Perceived hunger and satiety will be assessed by a questionnaire |
| Changes in gut microbiota composition | Baseline, 6, and 12 months | Fecal microbiota composition will be characterized by 16S rRNA gene amplicons sequencing using taxonomic and non-taxonomic based approaches. |
| Changes in gut microbiome functions | Baseline, 6, and 12 months | Fecal microbiome functions will be assessed through whole metagenomic sequencing, stool SCFAs and bile acids, and plasma metabolomics. |
| Changes in intestinal barrier integrity | Baseline, 6, and 12 months | Plasma lipopolysaccharide-binding protein and fecal calprotectin will be determined as measures of gut barrier integrity |
| Changes in quality of life | Baseline, 6, and 12 months | Quality of life will be measured by the a questionnaire |
Countries
Canada
Contacts
Primary ContactAndrea M Haqq, MD, MHS
Outcome results
None listed