Effect of Metformin on Vascular and Mitochondrial Function in Type 1 Diabetes

NCT ID: NCT01813929

Last Updated: 2022-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2017-03-24

Brief Summary

Insulin resistance (IR) is an important contributor to increased cardiovascular disease risk in type 1 diabetes (T1D). The purpose of this study is to measure the effect of metformin on insulin sensitivity, vascular function and compliance, and mitochondrial function in T1D. The long term goal is to identify novel non-glycemic approaches to managing cardiovascular disease risk in T1D. The results of this study may validate a novel approach to T1D treatment that could significantly improve current management of cardiovascular disease risk in this high risk population.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Metformin

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Six week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, 500/1000 for one week, and then 1000mg twice daily for the remainder of the 6 week intervention. If uptitration is not tolerated, max dose will be max tolerated dose of at least 500 mg twice daily.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Six-week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, and then the higher dose (850 mg) for the remainder of the 6 week intervention.

Interventions

Metformin

Six week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, 500/1000 for one week, and then 1000mg twice daily for the remainder of the 6 week intervention. If uptitration is not tolerated, max dose will be max tolerated dose of at least 500 mg twice daily.

Intervention Type: DRUG

Placebo

Six-week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, and then the higher dose (850 mg) for the remainder of the 6 week intervention.

Intervention Type: DRUG

Other Intervention Names

glucophage

Eligibility Criteria

Inclusion Criteria

• Age 20-59 years of age,
• Type 1 diabetes based on antibody-positivity, rapid persistent conversion to insulin requirement after diagnosis, absent C-peptide, or DKA at diagnosis, or a clinical course consistent with T1D,
• HbA1c 6.0 - 9.5, and
• Willing and able to commit to two 6 week-long periods of blinded medication followed by hyperinsulinemic euglycemic clamp, vascular testing, and muscle biopsies.

Exclusion Criteria

• Any comorbid condition associated with:

• inflammation,
• insulin Resistance, or
• dyslipidemia including:

1. cancer,

2. heart failure,

3. active or end stage liver disease,

4. kidney disease, or

5. rheumatological disease;

• Tobacco use;
• Pregnancy or women who are breastfeeding;
• Steroid use;
• Scheduled strenuous physical activity >3 days a week;
• Angina, known CAD, or any other cardiovascular or pulmonary disease;
• A history of COPD or asthma;
• Presence of systolic blood pressure >190 at rest or >250 with exercise, or diastolic pressure >95 at rest or >105 with exercise;
• Untreated thyroid disease;
• Proteinuria (urine protein >200 mg/dl) or a creatinine > 1.5 mg/dl (males) or 1.4 mg/dL (females), suggestive of severe renal disease;
• Severe Proliferative retinopathy;
• Niacin treatment;
• Administration of experimental agent for T1D within 30 days prior to screening;
• Recent (prior 6 months) or current metformin or thiazolidenedione use;
• Hypoglycemia unawareness or recurrent severe hypoglycemia (no symptoms of hypoglycemia with FSBS<40 and episodes of this severity >1 per week);
• Weight instability (weight change >5% in last 6 months);
• History of any organ transplant, including islet cell transplant;
• Current or prior infection with HIV, hepatitis B or hepatitis C or hepatic -insufficiency (AST or ALT > 2x the upper limits of normal);
• Any condition, medical or otherwise that would, in the opinion of the investigator, prevent complete participation in the study, or that would pose a significant hazard to the subject;
• History of substance abuse within the 12 months prior to screening.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

US Department of Veterans Affairs

FED

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Irene Schauer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Denver

Aurora, Colorado, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

11-0693

Identifier Type: -

Identifier Source: org_study_id