Coronary Heart Disease, Type 2 Diabetes
Conditions
Keywords
diastolic function, mitochondria, pioglitazone, pericardial fat
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.
Interventions
DRUGpioglitazone
45 mg per day for 6 months
Sponsors
Takeda Pharmaceuticals North America, Inc.
The University of Texas Health Science Center at San Antonio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin A1c | Baseline and 6-months Post Treatment | Change in hemoglobin A1c levels measured at 6 months |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone Only subjects with T2DM or non-diabetic subjects with coronary heart disease will receive Pioglitazone
pioglitazone: 45 mg per day for 6 months | 50 |
| Total | 50 |
Baseline characteristics
| Characteristic | Pioglitazone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 130 |
| other Total, other adverse events | 2 / 130 |
| serious Total, serious adverse events | 0 / 130 |
Outcome results
Primary
Change in E to A Ratio
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.
Time frame: Baseline and 6-months Post Treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in E to A Ratio | 1.04 Ratio | Standard Deviation 0.28 |
| E to A Ratio After Pioglitazone Treatment | Change in E to A Ratio | 1.25 Ratio | Standard Deviation 0.38 |
p-value: <0.01ANOVA
Primary
Myocardial Glucose Uptake
Measurement of change in myocardial glucose uptake from baseline to 6 months of treatment with pitoglitazone
Time frame: Baseline and 6-months Post Treatment
Population: Study participants who met eligibility criteria
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Myocardial Glucose Uptake | 0.24 uM/min/g | Standard Deviation 0.14 |
| E to A Ratio After Pioglitazone Treatment | Myocardial Glucose Uptake | 0.42 uM/min/g | Standard Deviation 0.13 |
Secondary
Change in Hemoglobin A1c
Change in hemoglobin A1c levels measured at 6 months
Time frame: Baseline and 6-months Post Treatment
Population: Enrolled subjects that meet eligibility criteria as type 2 diabetics or non diabetic subjects with coronary heart disease
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Change in Hemoglobin A1c | 6.7 percent | Standard Deviation 1.3 |
| E to A Ratio After Pioglitazone Treatment | Change in Hemoglobin A1c | 5.6 percent | Standard Deviation 0.8 |
p-value: <0.05ANOVA