Effect of Pioglitazone on Left Ventricular Diastolic Function in Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Effect of Pioglitazone on Left Ventricular Diastolic Function in Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00232362
• Other study ID #: L05-115
• Status: Withdrawn
• Phase: Phase 1
• First received: September 30, 2005
• Last updated: April 9, 2015
• Start date: June 2007
• Est. completion date: June 2008

Study information

• Verified date: April 2015
• Source: Texas Tech University Health Sciences Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This study is being done to determine if pioglitazone (Actos) is helpful to patients with type 2 diabetes and could possibly prevent harmful consequences of cardiovascular disease in diabetic patients.

Description:

Cross sectional and population-based studies indicate that at least one third of all patients with congestive heart failure (CHF) have a normal or near normal ejection fraction, which is thought to be secondary to diastolic dysfunction or failure. The mortality rates among the patients with diastolic failure ranges from 5-8% annually, as compared with 10-15% among patients with systolic heart failure. The morbidity associated with diastolic heart failure is similar to that of systolic heart failure. Several studies have shown that even simple Doppler evidence of diastolic dysfunction is an independent risk factor for the development of CHF and cardiac death and increased all cause mortality. Several studies indicate that left ventricular diastolic dysfunction (LVDD) represent the earliest preclinical manifestation of diabetic cardiomyopathy that can progress to symptomatic heart failure. Recent studies have demonstrated up to 60% of asymptomatic, normotensive patients with type 2 diabetes have LVDD when assessed by conventional echocardiography including the response to the Valsalva maneuver. A recent study using conventional Doppler, valsalva maneuver, color M-mode echocardiography and tissue doppler imaging assessed the diastolic dysfunction in asymptomatic normotensive patients with diabetes mellitus and found diastolic dysfunction in about 75% of these patients. Cardiovascular disease is the leading cause of death in patients with type 2 diabetes mellitus. Although diabetic patients have a large number of cardiovascular risk factors, like hyperlipidemia and hypertension, the diabetic cardiomyopathy occurs independent of these risk factors. Recently animal models have shown that LVDD may be prevented by chronic treatment with peroxisome-proliferator-activated receptors gamma (PPAR) agonists, like thiazolidinediones, in type 2 diabetic rats. Thiazolidinediones act through PPAR, but the exact mechanism by which they improve LVDD is not known. With this background knowledge, we wanted to study the effect of Pioglitazone, which is PPAR agonist and partial PPAR agonist, on the left ventricular diastolic dysfunction in type 2 diabetic human subjects, which has not been studied so far. If this therapy proves to have beneficial effect on the LVDD it will help in preventing the deleterious consequences of diastolic dysfunction in diabetic patients.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Patients with type 2 diabetes mellitus (DM)

2. Ages 18 to 65 years old

3. Patients with left ventricular diastolic dysfunction (LVDD) and ejection fraction (EF) > 50%

Exclusion Criteria:

1. Patients with uncontrolled hypertension

2. Patients with active myocardial ischemia with Canadian Cardiovascular Society (CCS) > II or known coronary artery disease (CAD)

3. Patients with atrial fibrillation

4. Patients with systolic heart failure

5. Patients with mitral regurgitation grade 2 or more

6. Patients with restrictive cardiomyopathy

7. Patients with constrictive pericarditis

8. Pregnant female patients

9. Recent stroke

10. Sepsis

11. Liver enzymes more than 2.5 times the normal

12. Hemoglobin < 11g/dl or hematocrit < 30%

13. Terminal cancer

14. Patients on fibrates group of lipid lowering agents

15. Patients already on pioglitazone or rosiglitazone

16. Patients who are placed in the control group may not be currently taking a medication in the glitazones drug class.

17. Current or prior use of Pioglitazone or Rosiglitazone within the preceding 6 months.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Pioglitazone (Actos)

• Anti-diabetic agent other than pioglitazone or rosiglitazone

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Texas Tech University Health Sciences Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in diastolic function parameters: early peak to late peak velocity (E/A) ratio
Primary	deceleration time (DT)
Primary	isovolumic relaxation time (IVRT)
Primary	E/A ratio percent change with Valsalva maneuver more than 40%
Primary	annular tissue Doppler velocity