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

Insulin Resistance Clinical Trial

Official title:

Fiber Supplementation and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance: Interactions With the Gut Microbiome.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04578652
• Other study ID #: RN. # 414120
• Status: Recruiting
• Phase: Phase 3
• Start date: October 22, 2021
• Est. completion date: September 2025

Study information

• Verified date: April 2024
• Source: University of Alberta
• Contact: Andrea M Haqq, MD, MHS
• Phone: 780-492-0015
• Email: haqq[@]ualberta.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Insulin Resistance
• Obesity
• Obesity, Childhood
• Obesity, Morbid
• Pediatric Obesity

Intervention

Drug:
• 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).

Dietary Supplement:
• 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.

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in HOMA-IR	Change in HOMA-IR value	Baseline, 6, and 12 months
Secondary	Changes in body weight	Body weight measured in kg	Baseline, 6, and 12 months
Secondary	Changes in body mass index (BMI)	BMI percentile and z-score according to age and sex will be estimated	Baseline, 6, and 12 months
Secondary	Changes in body composition	Body density using air-displacement plethysmography will be assessed to estimate fat mass and fat-free mass.	Baseline, 6, and 12 months
Secondary	Changes in inflammation	Markers of inflammation that will be measured are: high-sensitivity C-reactive protein, interleukin, tumor necrosis factor-alpha)	Baseline, 6, and 12 months
Secondary	Changes in metabolic function	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.	Baseline, 6, and 12 months
Secondary	Changes in satiety hormones	Markers of satiety that will be measured are: acylated ghrelin, peptide tyrosine tyrosine, GLP-1, leptin, and adiponectin.	Baseline, 6, and 12 months
Secondary	Changes in quality of life	Quality of life will be measured by the a questionnaire	Baseline, 6, and 12 months
Secondary	Changes in perceived hunger and satiety	Perceived hunger and satiety will be assessed by a questionnaire	Baseline, 6, and 12 months
Secondary	Changes in gut microbiota composition	Fecal microbiota composition will be characterized by 16S rRNA gene amplicons sequencing using taxonomic and non-taxonomic based approaches.	Baseline, 6, and 12 months
Secondary	Changes in gut microbiome functions	Fecal microbiome functions will be assessed through whole metagenomic sequencing, stool SCFAs and bile acids, and plasma metabolomics.	Baseline, 6, and 12 months
Secondary	Changes in intestinal barrier integrity	Plasma lipopolysaccharide-binding protein and fecal calprotectin will be determined as measures of gut barrier integrity	Baseline, 6, and 12 months