Mitochondrial-related Platelet Transcript Expression Levels in Pre-diabetic Subjects Randomized to Metformin or Placebo (MAP-2)

Metabolic Alterations in Platelet Study II

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.

Study Overview

• Status: Completed
• Conditions: Prediabetes
• Intervention / Treatment: Drug: Placebo; Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)
• All inclusion criteria will be checked on participants' first in-person visits.

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients on placebo.	Drug: Placebo; Placebo twice daily
Active Comparator: Active drug; Patients on Metformin, 850mg twice daily for 6mos.	Drug: Metformin; Metformin 850 mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome will be gene expression levels of mitofusin 2 and uncoupling protein 2	6 months

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Andrew S Weyrich, PhD, University of Utah

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: January 27, 2015
• First Submitted That Met QC Criteria: February 9, 2016
• First Posted (Estimate): February 15, 2016

Study Record Updates

• Last Update Posted (Estimate): January 30, 2017
• Last Update Submitted That Met QC Criteria: January 26, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Prediabetic State; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 1002