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

Obesity Clinical Trial

Official title:

The Gut Microbiome in Lean and Overweight Youth With Type 1 Diabetes and Novel Mechanism of Action of Metformin

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05414409
• Other study ID #: 15498
• Status: Recruiting
• Phase: Phase 2
• Start date: September 30, 2022
• Est. completion date: August 1, 2026

Study information

• Verified date: April 2023
• Source: Indiana University
• Contact: Heba M Ismail
• Phone: 317-274-2114
• Email: heismail[@]iu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 obesity as well as potential mechanisms to modify disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: August 1, 2026
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 11 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Obese youth 11-18 years of age with T1D at time of enrollment.

2. Lean youth 11-18 years of age with T1D at time of enrollment.

Exclusion Criteria:

1. Known monogenic forms of diabetes or Type 2 diabetes (confirmed clinically and by genetic/antibody testing).

2. History of ongoing infection or antibiotic treatment within the past month;

3. History of immune-compromise, recurrent infections, steroid intake (inhaled or oral forms) or other immunosuppressant use in the past 6 months.

4. History of chronic gastrointestinal disease, possible or confirmed celiac disease;

5. Participation in any research intervention trials within the past 3 months.

6. History of treatment or use of metformin, a type 2 diabetes medication.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Obesity
• Type 1 Diabetes

Intervention

Drug:
• Metformin
Metformin is an oral medication that improves insulin sensitivity.

Locations

Country	Name	City	State
United States	Indiana University School of Medicine	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Heba M. Ismail

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in the gut microbiome in lean and obese youth with type 1 diabetes	cross sectional comparison of stool microbiome using metagenomic sequencing data	2 years
Primary	Differences in the gut microbial metabolites in lean and obese youth with type 1 diabetes	The investigators will measure and compare the stool and serum short chain fatty acids using mass spectrometry	2 years
Primary	Differences in the gut microbial metabolites in lean and obese youth with type 1 diabetes	The investigators will measure and compare the stool and serum secondary bile acids using mass spectrometry	2 years
Primary	Changes in the gut microbiome in 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	3 years
Primary	Changes in the gut microbial metabolites in 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	3 years
Secondary	Differences in measures of C-peptide as a measure of beta cell health in lean and obese T1D youth	The investigators will measure serum C-peptide to calculate a ratio of proinsulin to C-peptide as a marker of beta cell health. These measures will then be compared between the lean and obese T1D youth.	2 years
Secondary	Differences in measures Proinsulin as a measure of beta cell health in lean and obese T1D youth	The investigators will measure serum proinsulin and calculate a ratio of proinsulin to C-peptide as a marker of beta cell health. These measures will then be compared between the lean and obese T1D youth.	2 years
Secondary	Differences in measures of insulin sensitivity in lean and obese T1D youth	Insulin sensitivity will be assessed in individuals using the estimated insulin sensitivity score (eIS), which is based on waist circumference (cm), HbA1c (%) and triglycerides (mg/dl)	2 years
Secondary	Changes in measures of C-peptide as a measure of beta cell health in obese T1D youth in response to metformin	Serum C-peptide will be used to calculate proinsulin to C-peptide ratio as a measure of beta cell health before and after metformin therapy	3 years
Secondary	Changes in measures of proinsulin as a measure of beta cell health in obese T1D youth in response to metformin	Serum proinsulin will be used to calculate proinsulin to C-peptide ratio as a measure of beta cell health before and after metformin therapy	3 years
Secondary	Changes in measures of insulin sensitivity in obese T1D youth in response to metformin	Estimated insulin sensitivity score will be used to assess response metformin therapy	3 years
Secondary	Changes in measures of beta cell function using a timed mixed meal tolerance test	Participants in the metformin trial will undergo a standard 2-hour mixed meal tolerance test at baseline and after 6 months of oral metformin therapy	3 years