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NCT Number: NCT01186250

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

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.

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Key information

Conditions

Cardiac Allograft Vasculopathy Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Stanford University School of Medicine

Stanford, California, 94305, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Heart transplant recipients, years 1-4 post-transplant
  • Age >= 18 years
  • Fasting TG/HDL ratio>=3.0 or Fasting TG>=150 mg/dL

Exclusion criteria

  • Diabetes mellitus
  • Severe liver dysfunction (ALT>=2.5 x upper limit of normal)
  • Severe renal dysfunction (GFR<30 or Stage IV CKD)
  • Moderate-severe fluid retention
  • Clinical or echocardiographic signs of left ventricular dysfunction
  • Contraindication to coronary angiography and/or IVUS

Treatment and study plan

pioglitazone

Drug

15mg pioglitazone taken daily for one month, 30mg pioglitazone taken daily for another month, 45mg pioglitazone taken daily for remaining ten months

Other names: Actos

Placebo

Drug

placebo taken daily for one year

Primary outcomes

  1. Insulin Levels Area Under Curve(AUC)

    Time frame: Baseline and 1 year

    Change from baseline in Insulin Levels During Oral Glucose Tolerance test at 1 year.

Secondary outcomes

  1. Change in Intimal Volume

    Time frame: baseline and 1 year

    Intimal volume is defined as external elastic membrane volume minus lumen (luminal) volume measured at the heart Catheterization and intravascular Ultrasound( IVUS)

  2. Change in Levels of Fasting Glucose at Baseline and 1 Year

    Time frame: Baseline and 1 year

    Oral Glucose Tolerance Test : blood was drawn for fasting plasma glucose and insulin levels, followed by ingestion of a solution containing 75grams of glucose. Repeat blood samples were collected for glucose and insulin levels at 30, 90, and 120 minutes after glucose ingestion. All glucose measurements were performed by the Clinical Translational Research Unit (CTRU) Stanford University.

  3. Change From Baseline in TG/HDL Ratio at One Year

    Time frame: Baseline and 1 year

    Triglyceride ratio to High Density Lipoprotien

  4. Change in Maximal Intimal Thickness(MIT) by Intravascular Unltrasound(IVUS)

    Time frame: Baseline and 1 year

    The change in maximal intimal thickness (MIT) from baseline to one year was recorded for several matched sites in the same coronary artery, the cross sections, predominantly in the left anterior descending coronary artery, from baseline to one-year follow-up, were studied. The IVUS cross sections were matched by using identifiable landmarks in the images, such as bifurcations or arterial calcification, or external landmarks, such as coronary veins or pericardium. In addition, the one-year IVUS studies were obtained with an angiographic roadmap of where the initial IVUS study was performed along the length of the vessel. The IVUS system auto pullback was performed at .5 mm/s from the mid-distal portion of the study vessel, where an easily identifiable landmark was visible (i.e., branchpoint). The following items were measured for each patient: maximal intimal thickness (MIT), intimal area (IA), and vessel area.

  5. Change From Baseline in ADMA (Asymmetric Dimethylarginine) at One Year.

    Time frame: Baseline and 1 year

    Competitive ELISA assay in Stanford laboratory.

  6. Change From Baseline in High-sensitivity C-reactive Protein (HsCRP) at One Year

    Time frame: Baseline and 1 year

    measure of low levels of C-reactive protein to identify low but persistent levels of inflammation

Sponsors and collaborators

Lead sponsor

Stanford University

Other

Registry information

Important dates

Study start
2010
Primary completion
2013
Study completion
2013
First posted
Aug 23, 2010
Registry last updated
Aug 18, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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