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

April 9, 2015 updated by: Texas Tech University Health Sciences Center
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Texas Tech University Health Sciences Center

Investigators

  • Principal Investigator: Chanwit Roongsritong, MD, TTUHSC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Study Completion (Anticipated)

June 1, 2008

Study Registration Dates

First Submitted

September 30, 2005

First Submitted That Met QC Criteria

September 30, 2005

First Posted (Estimate)

October 4, 2005

Study Record Updates

Last Update Posted (Estimate)

April 13, 2015

Last Update Submitted That Met QC Criteria

April 9, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • L05-115

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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