Myocardial Dysfunction in Type 2 Diabetes Mellitus (T2DM)

Phase 4

Completed

• Conditions: Type 2 Diabetes; Coronary Heart Disease
• Interventions: Drug: pioglitazone

• Registration Number: NCT01588470
• Lead Sponsor: The University of Texas Health Science Center at San Antonio

Brief Summary

The purpose of this study is to examine the existence of heart abnormalities in patients with diabetes and the effect of pioglitazone in correcting these abnormalities.

Detailed Description

PRIMARY OBJECTIVES

1. To quantitate myocardial insulin sensitivity using positron emission tomography (PET) with 18F-deoxyglucose in type 2 diabetes mellitus (T2DM) and control subjects.

2. To quantitate pericardial fat using magnetic resonance spectroscopy in T2DM and control subjects.

3. To quantitate cardiac function using magnetic resonance imaging and echocardiography in T2DM and control subjects.

4. To examine the effect of pioglitazone on myocardial insulin sensitivity, pericardial fat content, and cardiac function.

SECONDARY OBJECTIVES To examine the relationships between myocardial insulin sensitivity, pericardial fat content, and cardiac function.

Study Timeline

• Study Start: 2006-06
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Study First Submitted: 2012-03-19
• Study First Submitted QC: 2012-04-30
• Study First Posted: 2012-05-01
• Results First Submitted: 2016-02-17
• Status Verified: 2017-10
• Results First Submitted QC: 2017-10-31
• Last Update Submitted: 2017-10-31
• Results First Posted: 2017-12-06
• Last Update Posted: 2017-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

• Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.

• Patients may be of either sex. Female patients must be non-lactating and must either be at least one year post-menopausal, or be using adequate contraceptive precautions (i.e. oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients who have undergone a hysterectomy are eligible for participation in the study. Female patients (except for those patients who have undergone a hysterectomy or a bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period

• Patients must range in age from 18 to 75 years, inclusive.

• Patients with type 2 diabetes must be drug naïve, receiving monotherapy with metformin or with a sulfonylurea, or combination therapy with both: metformin & sulfonylurea.

• Patients must have the following laboratory values:

  • Hematocrit ≥ 34 vol%
  • Serum creatinine ≤ 1.8 mg/dl
  • AST (SGOT) ≤ 2.5 times upper limit of normal
  • ALT (SGPT) ≤ 2.5 times upper limit of normal
  • Alkaline phosphatase ≤ 2 times upper limit of normal

• Patients must have been on a stable dose of allowed chronic medications for 30 days prior to entering the study.

• Only subjects whose body weight has been stable (±3-4 pounds) over the three months prior to study will be included.

Exclusion Criteria

• Patients must not have type 1 diabetes.
• Patients must not be receiving any medications with known adverse effects on glucose tolerance (except metformin or a sulfonylurea) unless the patient has been on stable doses of such agents for the past three months before entry into the study. Patients may be taking stable doses of estrogens or other hormonal replacement therapy, if the patient has been on these agents for the prior three months. Patients taking systemic glucocorticoids are excluded.
• Patients with a history of clinically significant heart disease (New York Heart Classification greater than class 2; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
• Patients with hematocrit < 34% will be excluded.
• Patient who were exposed to any procedure involves radiation exposure and his total radiation dose equivalent exceeds 5 rem during the past year will be excluded from the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pioglitazone	pioglitazone	Only subjects with T2DM or non-diabetic subjects with coronary heart disease will receive Pioglitazone

Primary Outcome Measures

Name	Time	Method
Change in E to A Ratio	Baseline and 6-months Post Treatment	The E to A ratio is a marker of the function of the left ventricle of the heart. It represents the ratio of peak velocity flow in early diastole (the E wave) to peak velocity flow in late diastole caused by the atrial contraction (the A wave) This is measured using ultrasound-based cardiac imaging. In a healthy heart the E velocity is greater than the A velocity.
Myocardial Glucose Uptake	Baseline and 6-months Post Treatment	Measurement of change in myocardial glucose uptake from baseline to 6 months of treatment with pitoglitazone

Secondary Outcome Measures

Name	Time	Method
Change in Hemoglobin A1c	Baseline and 6-months Post Treatment	Change in hemoglobin A1c levels measured at 6 months