Clinical trial NCT01186250: Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation
Official title: Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiac Allograft Vasculopathy
Keywords: cardiac allograft vasculopathy
pioglitazone
insulin resistance
heart transplant
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2010-08-23
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Insulin Levels Area Under Curve(AUC)
timeFrame: Baseline and 1 year
Secondary outcomes:
measure: Change in Intimal Volume
timeFrame: baseline and 1 year
measure: Change in Levels of Fasting Glucose at Baseline and 1 Year
timeFrame: Baseline and 1 year
measure: Change From Baseline in TG/HDL Ratio at One Year
timeFrame: Baseline and 1 year
measure: Change in Maximal Intimal Thickness(MIT) by Intravascular Unltrasound(IVUS)
timeFrame: Baseline and 1 year
measure: Change From Baseline in ADMA (Asymmetric Dimethylarginine) at One Year.
timeFrame: Baseline and 1 year
measure: Change From Baseline in High-sensitivity C-reactive Protein (HsCRP) at One Year
timeFrame: Baseline and 1 year
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Kiran Khush
role: PRINCIPAL_INVESTIGATOR
References: