Clinical trial NCT02682121: Mitochondrial-related Platelet Transcript Expression Levels in Pre-diabetic Subjects Randomized to Metformin or Placebo
Official title: Metabolic Alterations in Platelet Study II
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prediabetes
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2016-02-15
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


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)
* 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).

Primary outcomes:
measure: The primary outcome will be gene expression levels of mitofusin 2 and uncoupling protein 2
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Andrew S Weyrich, PhD
role: PRINCIPAL_INVESTIGATOR
References: