Mitochondrial-related Platelet Transcript Expression Levels in Pre-diabetic Subjects Randomized to Metformin or Placebo

NCT ID: NCT02682121

Last Updated: 2017-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2017-01-31

Brief Summary

Diabetes mellitus (DM) imposes an approximate 2-fold increased risk of atherothrombosis. Patients with type 2 DM have a 2- to 4-fold increase in the risk of coronary artery disease (CAD) and atherothrombotic complications. Current evidence indicates that altered platelet function and "reactivity" are key determinants of arterial and venous thrombosis in metabolic syndromes. In addition, venous thrombosis and pulmonary embolism are associated with increased body mass index, a common feature of type 2 DM and the metabolic syndrome. Altered platelet behavior, function, and phenotype may be critical factors in these thrombotic complications as well. The mechanisms that lead to altered phenotype and function of platelets in DM, and that underlie heightened contributions of platelets to thrombotic complications in type 2 DM, are nevertheless incompletely understood. In this project, the investigators will prospectively determine if clinical intervention with metformin--a commonly-used therapeutic agent that reduces blood glucose, promotes weight loss, and improves lipid profiles--reverses platelet reprogramming and hyperreactivity in obese subjects with impaired fasting glucose and thus, at-risk for type 2 DM.

In addition to metformin, all participants will be given lifestyle modification (LSM) education on diet and physical activity, followed by guidance on how to adhere to the LSM, depending on random assignment to intervention group (education only (n=26) vs. implementation intentions alone (n=27) vs. implementation intentions with partner (n=27)). The LSM coaching for different intervention groups will allow the investigators to test whether there are more effective ways for adherence than others. Participants in these three LSM intervention groups will be further randomized to either Metformin (n=40) or Placebo (n=40), such that participants in the three LSM groups will be randomly and evenly distributed across the two study medication groups.

Conditions

Prediabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Patients on placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo twice daily

Active drug

Patients on Metformin, 850mg twice daily for 6mos.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin 850 mg twice daily

Interventions

Metformin

Metformin 850 mg twice daily

Intervention Type: DRUG

Placebo

Placebo twice daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• age≥18 years
• BMI>25 kg/m2
• fasting plasma glucose 100-125 mg/dL, AND/OR Hemoglobin-A1C between 5.5 and 6.4%, AND/OR post-load glucose between 140 and 199 mg/dL on a 2-hour Oral Glucose Tolerance Test (OGTT)

Exclusion Criteria

• unwilling to accept treatment assignment by randomization
• participation in another clinical research trial
• history of myocardial infarction or stroke
• significant arrhythmia (e.g. atrial fibrillation)
• active thromboembolic disease
• inflammatory bowel disease
• serum creatinine levels greater than or equal to 1.5 mg/dL in males or greater than or equal to 1.4 mg/dL in females
• known hypersensitivity to metformin hydrochloride or any of its components
• acute or chronic metabolic acidosis
• inability to participate in lifestyle modifications
• pregnancy; other glucose-lowering or diabetic therapy
• systemic glucocorticoids
• prescription weight loss medications
• or otherwise deemed unsuitable by study investigators (e.g. unable to complete follow-up visits, alcohol abuse, etc).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Matthew Rondina, MD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrew S Weyrich, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

1002

Identifier Type: -

Identifier Source: org_study_id