Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation

Heart Transplant Clinical Trial

Official title:

Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01186250
• Other study ID #: SU-05282010-6202
• Secondary ID: CTRU protocol 13
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 19, 2010
• Last updated: March 26, 2013
• Start date: July 2010
• Est. completion date: December 2013

Study information

• Verified date: March 2013
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the benefit of using the FDA-approved insulin-sensitizing agent, Pioglitazone, on human heart transplant recipients. The objectives of this project are to (1) determine if pioglitazone effectively treats insulin resistance in heart transplant recipients, and (2) to determine whether pioglitazone therapy after heart transplantation impacts the development or progression of cardiac allograft vasculopathy (CAV), a form of chronic rejection after heart transplantation.

Description:

CAV, a rapidly progressive obliterative disease involving the graft coronary arteries, is the leading cause of morbidity and mortality beyond the first year after heart transplantation. This common complication occurs in almost half of recipients within 3 years after heart transplantation, and is associated with high rates of graft failure and mortality. Clinical care of heart transplant recipients in the current era is greatly limited by the lack of effective treatment options to prevent or retard the progression of CAV. CAV appears to be strongly associated with the state of insulin resistance, which is present in over half of heart transplant recipients and is characterized by metabolic abnormalities including glucose intolerance, dyslipidemia, endothelial dysfunction, and high levels of circulating inflammatory markers. Insulin resistance can be effectively treated with pioglitazone, a TZD compound which directly affects tissue insulin sensitivity. In this study, we will enroll 32 insulin-resistant heart transplant recipients and will randomize them to pioglitazone or placebo for a one-year period. We will determine the efficacy of pioglitazone for the treatment of insulin resistance and prevention of the development and progression of CAV after heart transplantation. The data generated from this study will provide important preliminary data for future, larger-scale clinical investigations.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 32
• Est. completion date: December 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Heart transplant recipients, years 1-4 post-transplant

2. Age >= 18 years

3. Fasting TG/HDL ratio>=3.0 or Fasting TG>=150 mg/dL

Exclusion Criteria:

1. Diabetes mellitus

2. Severe liver dysfunction (ALT>=2.5 x upper limit of normal)

3. Severe renal dysfunction (GFR<30 or Stage IV CKD)

4. Moderate-severe fluid retention

5. Clinical or echocardiographic signs of left ventricular dysfunction

6. Contraindication to coronary angiography and/or IVUS

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Transplant
• Vascular Diseases

Intervention

Drug:
• Pioglitazone
15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months
• Placebo
placebo taken daily for one year

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin levels during oral glucose tolerance test		Baseline and 1 year	No
Secondary	mean coronary artery plaque volume		baseline and 1 year	No
Secondary	Change in levels of fasting glucose, lipids, ADMA, and hs-CRP		Baseline and 1 year	No
Secondary	Change in levels of circulating markers of inflammation		Baseline and 1 year	No