Fiber and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance

Phase 3

Recruiting

• Conditions: Obesity, Childhood; Insulin Resistance
• Interventions: Drug: Metformin 850 mg oral tablet bid; Dietary Supplement: Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.

• Registration Number: NCT04578652
• Lead Sponsor: University of Alberta

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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Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-01
• Study First Submitted QC: 2020-10-01
• Study First Posted: 2020-10-08
• Study Start: 2021-10-22
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-14
• Last Update Posted: 2025-04-15
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MET	Metformin 850 mg oral tablet bid	MET (850 mg po bid - standard of care) + Fiber placebo daily
FIBER + MET	Metformin 850 mg oral tablet bid	Fiber supplementation \[35g fiber daily\] + MET 850 mg po bid
FIBER	Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.	Fiber supplementation \[35g fiber daily\] + MET placebo po bid
FIBER + MET	Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.	Fiber supplementation \[35g fiber daily\] + MET 850 mg po bid

Primary Outcome Measures

Name	Time	Method
Changes in HOMA-IR	Baseline, 6, and 12 months	Change in HOMA-IR value

Secondary Outcome Measures

Name	Time	Method
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 body weight	Baseline, 6, and 12 months	Body weight measured in kg
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 quality of life	Baseline, 6, and 12 months	Quality of life will be measured by the a questionnaire
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

Trial Locations

Locations (1)

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada