Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Insulin Levels Area Under Curve(AUC)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Heart transplant recipients, years 1-4 post-transplant
- •Age >= 18 years
- •Fasting TG/HDL ratio>=3.0 or Fasting TG>=150 mg/dL
排除标准
- •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
研究组 & 干预措施
Pioglitazone
Pioglitazone
干预措施: Pioglitazone (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Insulin Levels Area Under Curve(AUC)
时间窗: Baseline and 1 year
Change from baseline in Insulin Levels During Oral Glucose Tolerance test at 1 year.
次要结局
- Change in Intimal Volume(baseline and 1 year)
- Change From Baseline in High-sensitivity C-reactive Protein (HsCRP) at One Year(Baseline and 1 year)
- Change in Maximal Intimal Thickness(MIT) by Intravascular Unltrasound(IVUS)(Baseline and 1 year)
- Change From Baseline in ADMA (Asymmetric Dimethylarginine) at One Year.(Baseline and 1 year)
- Change From Baseline in TG/HDL Ratio at One Year(Baseline and 1 year)
- Change in Levels of Fasting Glucose at Baseline and 1 Year(Baseline and 1 year)
研究者
Kiran Khush
Assistant Professor of Medicine
Stanford University