Insulin Clamp Ancillary Study for Assessment of Insulin Resistance

Study Overview
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Brief Summary
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Insulin Clamp Ancillary study for Assessment of Insulin Resistance will be conducted as a sub-study to the main protocol, Metformin Therapy for Overweight Adolescents With Type 1 Diabetes (NCT01881828). The purpose of this ancillary study is to assess if metformin will improve tissue-specific insulin resistance (IR) in type 1 diabetes using a hyperinsulinemic euglycemic clamp; a 3-month randomized trial comparing metformin versus placebo in 12 to <20 year olds with BMI >85th percentile ( total daily insulin dose >0.7 units/kg, and HbA1c 7.0%-9.9%).

Official Title
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Metformin Therapy for Overweight Adolescents With Type 1 Diabetes (T1D)--Insulin Clamp Ancillary Study for Assessment of Insulin Resistance

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Meets eligibility criteria of the main study, Metformin Therapy for Overweight Adolescents With Type 1 Diabetes (NCT01881828). Exclusion Criteria: 1. Low hemoglobin or hematocrit as defined by each local institution's rules for insulin clamps or if no institutional requirements a Hematocrit <30% or hemoglobin <10 gm/dL

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Oral Placebo<br>A central pharmacy will compound a placebo to match the metformin tablets. The placebo product will contain the following components: Micosolle™, silica based excipient Silicified Micro Crystalline Cellulose, National Formulary Safflower Oil, United States Pharmacopeia K-30 Povidone Powder Magnesium Stearate, National Formulary (Vegetable source) Fumed Silica, National Formulary | Drug: Placebo<br> <br> |
| Experimental: Metformin<br>Metformin 2000 mg per day | Drug: Metformin<br>* The strength of each tablet will be 500 mg. Participants will build up to a daily dose over four weeks by taking one tablet per day for 7 days, one tablet twice daily for 7 days, one tablet in the morning and 2 tablets at night for 7 days, and then 2 tablets in the morning and 2 tablets at night, daily throughout the remainder of the study treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin resistance (IR) from baseline to 13 weeks | Hyperinsulinemic euglycemic clamp to assess metformin's impact on muscle IR via glucose infusion rate (GIR). | 0-13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hepatic IR from baseline to 13 weeks | Graded hyperinsulinemic euglycemic clamp with glucose and glycerol isotopes to assess metformin's impact on: • Hepatic IR | 0-13 weeks | 
| Change in Adipose IR from baseline to 13 weeks | Graded hyperinsulinemic euglycemic clamp with glucose and glycerol isotopes to assess metformin's impact on: • Adipose IR | 0-13 weeks |