Clinical trial NCT01588470: Myocardial Dysfunction in Type 2 Diabetes Mellitus (T2DM)
Official title: Myocardial Dysfunction in Type 2 Diabetes Mellitus (T2DM) - Role of Intramyocellular Lipid Content and Mitochondrial Dysfunction in Myocardial Insulin Resistance and Their Correction With Pioglitazone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Coronary Heart Disease
Keywords: diastolic function
mitochondria
pioglitazone
pericardial fat
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: Takeda Pharmaceuticals North America, Inc.
First posted: 2012-05-01
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: this study includes single arm intervention with pioglitazone. T2DM individuals will be studied at baseline and after 6 months treatment.

as a reference group, healthy subjects will be studied in cross sectional fashion. Because healthy subjects will not be treated nor restudied at 6 months, they can not be considered a separate arm in the study but rather a reference group
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in E to A Ratio
timeFrame: Baseline and 6-months Post Treatment
measure: Myocardial Glucose Uptake
timeFrame: Baseline and 6-months Post Treatment
Secondary outcomes:
measure: Change in Hemoglobin A1c
timeFrame: Baseline and 6-months Post Treatment
Other outcomes:
Locations:
Study officials:
affiliation: University of Texas
name: Ralph A DeFronzo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clarke GD, Solis-Herrera C, Molina-Wilkins M, Martinez S, Merovci A, Cersosimo E, Chilton RJ, Iozzo P, Gastaldelli A, Abdul-Ghani M, DeFronzo RA. Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes. Diabetes Care. 2017 Nov;40(11):1530-1536. doi: 10.2337/dc17-0078. Epub 2017 Aug 28.