Effect of Metformin on Vascular and Mitochondrial Function in Type 1 Diabetes
MeT1
1 other identifier
interventional
23
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_4
Started Jun 2011
Longer than P75 for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2011
CompletedFirst Submitted
Initial submission to the registry
September 28, 2012
CompletedFirst Posted
Study publicly available on registry
March 19, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 24, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
March 24, 2017
CompletedResults Posted
Study results publicly available
January 21, 2022
CompletedJanuary 21, 2022
December 1, 2021
5.8 years
September 28, 2012
October 7, 2021
December 21, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Insulin Sensitivity by Hyperinsulinemic Euglycemic Clamp
Determine the effect of metformin on insulin sensitivity in T1D. Reported measure is glucose infusion rate during hyperinsulinemic euglycemic clamp normalized to total body weight. For this measure, insulin was infused at 40 mU/m2 surface area. Blood sugar wass checked every 5 minutes and glucose infusion adjusted to maintain glucose level at 90 mg/dL for 2 hours. The glucose infusion rate for the final 30 minutes is reported as GIR (aka M-value or glucose disposal rate) in mg glucose/kg\*min. A higher value corresponds to greater sensitivity to insulin. There is no strictly defined normal range.
End of each 6 week intervention period
Flow-mediated Brachial Artery Dilation
Measure of endothelial function by brachial ultrasound of the percent dilation after 5 minutes of occlusion.
End of each 6 week intervention period
Secondary Outcomes (22)
Arterial Stiffness by PWV
End of each 6 week intervention period
Arterial Stiffness by AI@75
End of each 6 week intervention period
Mitochondrial Measures: Oxygen Consumption
End of each 6 week intervention period
Mitochondrial Measures: Protein Expression Levels of Electron Transport Chain Complexes
End of each 6 week intervention period
Inflammatory Marker: hsCRP
End of each 6 week intervention period
- +17 more secondary outcomes
Other Outcomes (6)
Vascular Markers: PAI-1
End of each 6 week intervention period
Vascular Markers: Exploratory
End of each 6 week intervention period
Oxidative Stress Markers
End of each 6 week intervention period
- +3 more other outcomes
Study Arms (2)
Metformin
EXPERIMENTALPlacebo
PLACEBO COMPARATORInterventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- Any comorbid condition associated with:
- inflammation,
- insulin Resistance, or
- dyslipidemia including:
- cancer,
- heart failure,
- active or end stage liver disease,
- kidney disease, or
- 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;
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Colorado, Denverlead
- US Department of Veterans Affairscollaborator
Study Sites (1)
University of Colorado Denver
Aurora, Colorado, 80045, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Irene Schauer, MD
- Organization
- University of Colorado Denver
Study Officials
- PRINCIPAL INVESTIGATOR
Irene Schauer, MD, PhD
University of Colorado, Denver
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 28, 2012
First Posted
March 19, 2013
Study Start
June 1, 2011
Primary Completion
March 24, 2017
Study Completion
March 24, 2017
Last Updated
January 21, 2022
Results First Posted
January 21, 2022
Record last verified: 2021-12