The Gut Microbiome in Type 1 Diabetes and Mechanism of Metformin Action

NCT05414409 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 154981K23DK129799
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

Ovwerweight and obesity prevalence in persons with T1D has increased, which further complicates management and risk for complications. The proposed study is relevant to public health because it helps us understand the role of the gut microbiome in disease pathophysiology in T1D youth with overweight and obesity as well as potential mechanisms to modify disease.

Conditions

Type 1 Diabetes; Obesity

Outcome Measures

Primary Outcomes (5)

• Differences in the gut microbiome in lean and overweight/obese youth with type 1 diabetes

  cross sectional comparison of stool microbiome using metagenomic sequencing data

  Baseline

• Differences in the gut microbial metabolites in lean and overweight/obese youth with type 1 diabetes

  The investigators will measure and compare the stool and serum short chain fatty acids using mass spectrometry

  Baseline

• Differences in the gut microbial metabolites in lean and overweight/obese youth with type 1 diabetes

  The investigators will measure and compare the stool and serum secondary bile acids using mass spectrometry

  Baseline

• Changes in the gut microbiome in overweight/obese youth with type 1 diabetes in response to metformin

  longitudinal comparison before and after taking metformin for 6 months, stool samples will be collected at baseline, 3 months and 6 months and sequenced for microbiome profile using metagenomic sequencing

  Baseline, Month 3, and Month 6

• Changes in the gut microbial metabolites in overweight/obese youth with type 1 in response to metformin

  The investigators will measure and compare the stool and serum metabolites (short chain fatty acids and secondary bile acids) before, during and after 6 months of daily metformin therapy using mass spectrometry

  Baseline, Month 3, and Month 6

Secondary Outcomes (7)

• Differences in measures of C-peptide as a measure of beta cell health in lean and overweight/obeseT1D youth

  Baseline

• Differences in measures Proinsulin as a measure of beta cell health in lean and overweight/obeseT1D youth

  Baseline

• Differences in measures of insulin sensitivity in lean and overweight/obese T1D youth

  Baseline

• Changes in measures of C-peptide as a measure of beta cell health in overweight/obese T1D youth in response to metformin

  Baseline, Month 3, and Month 6

• Changes in measures of proinsulin as a measure of beta cell health in overweight/obese T1D youth in response to metformin

  Baseline, Month 3, and Month 6

Study Arms (2)

Comparison of microbiome by BMI Category

NO INTERVENTION

The gut microbiome and metabolites of 42 lean and 42 overweight/obese youth with type 1 diabetes will be evaluated cross-sectionally.

Metformin

EXPERIMENTAL

This is a group of 30 youth with type 1 diabetes and overweight/obesity who will receive metformin for 6 months.

Drug: Metformin

Interventions

Metformin DRUG

Metformin is an oral medication that improves insulin sensitivity.

Metformin

Eligibility Criteria

• Age: 11 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Overweight/obese youth 11-18 years of age with T1D at time of enrollment.
• Lean youth 11-18 years of age with T1D at time of enrollment.

You may not qualify if:

• Known monogenic forms of diabetes or Type 2 diabetes (confirmed clinically and by genetic/antibody testing).
• History of ongoing infection or antibiotic treatment within the past month;
• History of immune-compromise, recurrent infections, steroid intake (inhaled or oral forms) or other immunosuppressant use in the past 6 months.
• History of chronic gastrointestinal disease and active within the past 6 months, possible or confirmed celiac disease.
• Participation in any research intervention trials within the past 3 months.
• History of treatment or use of metformin, a type 2 diabetes medication.

Sponsors & Collaborators

• Heba M. Ismail: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Obesity

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Central Study Contacts

Heba M Ismail

CONTACT

317-274-2114; heismail@iu.edu

HI Team

CONTACT

317-274-2114; hiteam@iu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Model Details: The investigators will examine the differences in the gut microbiome between lean and overweight/obese youth with type 1 diabetes and then enroll the overweight/obese youth with type 1 diabetes into the clinical trial to receive metformin as an intervention.

Study Record Dates

• First Submitted: May 31, 2022
• First Posted: June 10, 2022
• Study Start: September 30, 2022
• Primary Completion (Estimated): November 2, 2026
• Study Completion (Estimated): November 2, 2026
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)