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

NCT ID: NCT04578652

Last Updated: 2025-11-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-22
• Study Completion Date: 2026-09-30

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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Conditions

Obesity, Childhood; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

MET

MET (850 mg po bid - standard of care) + Fiber placebo daily

Group Type: ACTIVE_COMPARATOR

Metformin 850 mg oral tablet bid

Intervention Type: 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).

FIBER

Fiber supplementation \[35g fiber daily\] + MET placebo po bid

Group Type: ACTIVE_COMPARATOR

Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.

Intervention Type: 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.

FIBER + MET

Fiber supplementation \[35g fiber daily\] + MET 850 mg po bid

Group Type: EXPERIMENTAL

Metformin 850 mg oral tablet bid

Intervention Type: 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).

Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.

Intervention Type: 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.

Interventions

Metformin 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).

Intervention Type: DRUG

Supplemental 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.

Intervention Type: DIETARY_SUPPLEMENT

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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alberta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrea M Haqq, MD, MHS

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

University of Alberta

Edmonton, Alberta, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Andrea M Haqq, MD, MHS

Role: CONTACT

haqq@ualberta.ca

780-492-0015

Facility Contacts

Andrea M Haqq, MD, MHS

Role: primary

haqq@ualberta.ca

780-492-0015

References

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.

Reference Type: DERIVED

PMID: 40637175 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33596993 (View on PubMed)

Other Identifiers

RN. # 414120

Identifier Type: -

Identifier Source: org_study_id