Back to resultsThe Gut Microbiome in Type 1 Diabetes and Mechanism of Metformin Action
Primary Purpose
Type 1 Diabetes, Obesity
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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, 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.
Sites / Locations
- Indiana University School of MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Comparison of microbiome by BMI Category
Metformin
Arm Description
The gut microbiome and metabolites of 42 lean and 42 obese youth with type 1 diabetes will be evaluated cross-sectionally.
This is a group of 30 youth with type 1 diabetes and obesity who will receive metformin for 6 months.
Outcomes
Primary Outcome Measures
Differences in the gut microbiome in lean and obese youth with type 1 diabetes
cross sectional comparison of stool microbiome using metagenomic sequencing data
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
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
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
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
Secondary Outcome Measures
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.
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.
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)
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
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05414409
Brief Title
The Gut Microbiome in Type 1 Diabetes and Mechanism of Metformin Action
Official Title
The Gut Microbiome in Lean and Overweight Youth With Type 1 Diabetes and Novel Mechanism of Action of Metformin
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 30, 2022 (Actual)
Primary Completion Date
August 1, 2025 (Anticipated)
Study Completion Date
August 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Heba M. Ismail
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes, Obesity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
The investigators will examine the differences in the gut microbiome between lean and obese youth with type 1 diabetes and then enroll the obese youth with type 1 diabetes into the clinical trial to receive metformin as an intervention.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
114 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Comparison of microbiome by BMI Category
Arm Type
No Intervention
Arm Description
The gut microbiome and metabolites of 42 lean and 42 obese youth with type 1 diabetes will be evaluated cross-sectionally.
Arm Title
Metformin
Arm Type
Experimental
Arm Description
This is a group of 30 youth with type 1 diabetes and obesity who will receive metformin for 6 months.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Metformin is an oral medication that improves insulin sensitivity.
Primary Outcome Measure Information:
Title
Differences in the gut microbiome in lean and obese youth with type 1 diabetes
Description
cross sectional comparison of stool microbiome using metagenomic sequencing data
Time Frame
2 years
Title
Differences in the gut microbial metabolites in lean and obese youth with type 1 diabetes
Description
The investigators will measure and compare the stool and serum short chain fatty acids using mass spectrometry
Time Frame
2 years
Title
Differences in the gut microbial metabolites in lean and obese youth with type 1 diabetes
Description
The investigators will measure and compare the stool and serum secondary bile acids using mass spectrometry
Time Frame
2 years
Title
Changes in the gut microbiome in obese youth with type 1 diabetes in response to metformin
Description
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
Time Frame
3 years
Title
Changes in the gut microbial metabolites in obese youth with type 1 in response to metformin
Description
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
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Differences in measures of C-peptide as a measure of beta cell health in lean and obese T1D youth
Description
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.
Time Frame
2 years
Title
Differences in measures Proinsulin as a measure of beta cell health in lean and obese T1D youth
Description
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.
Time Frame
2 years
Title
Differences in measures of insulin sensitivity in lean and obese T1D youth
Description
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)
Time Frame
2 years
Title
Changes in measures of C-peptide as a measure of beta cell health in obese T1D youth in response to metformin
Description
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
Time Frame
3 years
Title
Changes in measures of proinsulin as a measure of beta cell health in obese T1D youth in response to metformin
Description
Serum proinsulin will be used to calculate proinsulin to C-peptide ratio as a measure of beta cell health before and after metformin therapy
Time Frame
3 years
Title
Changes in measures of insulin sensitivity in obese T1D youth in response to metformin
Description
Estimated insulin sensitivity score will be used to assess response metformin therapy
Time Frame
3 years
Title
Changes in measures of beta cell function using a timed mixed meal tolerance test
Description
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
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
11 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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, 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Heba M Ismail
Phone
317-274-2114
Email
heismail@iu.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Akane Hawpe
Phone
317-274-2114
Email
ahawpega@iu.edu
Facility Information:
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heba Ismail
Phone
317-278-7856
Email
heismail@iu.edu
First Name & Middle Initial & Last Name & Degree
Katelyn Hagen
Phone
317-278-7042
Email
hagenka@iu.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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The Gut Microbiome in Type 1 Diabetes and Mechanism of Metformin Action
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