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Effect of Metformin on Vascular and Mitochondrial Function in Type 1 Diabetes (MeT1)

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ClinicalTrials.gov Identifier: NCT01813929
Recruitment Status : Active, not recruiting
First Posted : March 19, 2013
Last Update Posted : February 10, 2021
Sponsor:
Collaborator:
US Department of Veterans Affairs
Information provided by (Responsible Party):
University of Colorado, Denver

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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: Metformin Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Metformin on Vascular and Mitochondrial Function in Type 1 Diabetes
Study Start Date : June 2011
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: Metformin Drug: 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.
Other Name: glucophage

Placebo Comparator: Placebo 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.




Primary Outcome Measures :
  1. Insulin Sensitivity by hyperinsulinemic euglycemic clamp [ Time Frame: End of each 6 week intervention period ]
    Determine the effect of metformin on insulin sensitivity in T1D.

  2. Flow-mediated brachial artery dilation [ Time Frame: End of each 6 week intervention period ]
    Measure of endothelial function


Secondary Outcome Measures :
  1. Arterial stiffness [ Time Frame: End of each 6 week intervention period ]
    PWV and AI by Sphygmacor

  2. Mitochondrial measures [ Time Frame: End of each 6 week intervention period ]
    Mito content and electron transport chain complexes, oxygen consumption with various substrates and max uncoupled O2 consumption. oxidant generation

  3. Metabolic, inflammatory, vascular, and oxidative stress markers [ Time Frame: End of each 6 week intervention period ]
    glucose, fatty acids, triglycerides, cholesterol, glycerol, insulin, lactate, counterregulatory hormones, IL6, TNF alpha, hsCRP, PAI-1, adiponection, TBARs, ICAM, endothelin-1, GSSG:GSH ratio

  4. Heart rate variability [ Time Frame: End of each 6 week intervention period ]
    measure of autonomic function



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Ages Eligible for Study:   25 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01813929


Locations
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United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
US Department of Veterans Affairs
Investigators
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Principal Investigator: Irene Schauer, MD, PhD University of Colorado, Denver
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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01813929    
Other Study ID Numbers: 11-0693
First Posted: March 19, 2013    Key Record Dates
Last Update Posted: February 10, 2021
Last Verified: February 2021
Keywords provided by University of Colorado, Denver:
Diabetes
Insulin
Metformin
Vascular
Vessels
Type 1
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs