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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Kiran Khush, Stanford University
ClinicalTrials.gov Identifier:
NCT01186250
First received: August 19, 2010
Last updated: March 26, 2013
Last verified: March 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Heart Transplant
 Drug: Pioglitazone
Drug: Placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Insulin levels during oral glucose tolerance test [ Time Frame: Baseline and 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • mean coronary artery plaque volume [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
  • Change in levels of fasting glucose, lipids, ADMA, and hs-CRP [ Time Frame: Baseline and 1 year ] [ Designated as safety issue: No ]
  • Change in levels of circulating markers of inflammation [ Time Frame: Baseline and 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: July 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
Pioglitazone
 Drug: Pioglitazone
15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months
Other Name: Actos
Placebo Comparator: Arm 2
Placebo
 Drug: Placebo
placebo taken daily for one year

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01186250

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Kiran Khush Stanford University
  More Information

No publications provided

Responsible Party: Kiran Khush, Assistant Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01186250     History of Changes
Other Study ID Numbers: SU-05282010-6202, CTRU protocol 1314, IRB protocol 19373
Study First Received: August 19, 2010
Last Updated: March 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Stanford University:
cardiac allograft vasculopathy
pioglitazone
insulin resistance
heart transplant

Additional relevant MeSH terms:
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013