Imaging of Histone Deacetylase in the Heart
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- 11C-Martinostat Binding
研究概览
简要总结
The overall goal of this PET-MR imaging trial is to evaluate 11C-Martinostat, a histone deacetylase targeted radioligand, in patients with aortic stenosis, individuals with diabetes, and healthy volunteers.
详细描述
Histone deacetylases (HDACs), a class of epigenetic enzymes, play an important role in the pathophysiology of heart failure, including development of left ventricular hypertrophy and myocardial fibrosis. Preclinical data demonstrate the importance of HDAC inhibition in attenuating these pathological processes and maintaining the integrity of the myocardium. However, the role of HDACs in the human heart, and the utility of HDAC inhibition remains unknown. Therefore, a noninvasive method to detect HDAC activity in the human heart in healthy individuals and patients with heart disease may be of major medical and public health value to help determine prognosis, direct therapy, and guide the development of novel therapies for heart failure. The investigators have recently developed a novel radiotracer, 11C-Martinostat, which binds with high affinity to class I HDACs. The objective of this protocol is to assess the utility of 11C-Martinostat PET-MR to detect HDAC expression in the hearts of healthy individuals and patients with severe aortic stenosis or diabetes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Group 1: Healthy Volunteers (n = 30)
- •Healthy adults with no known history of medical disease
- •Age 18-85 years
- •No history cardiovascular disease
- •Ability to provide informed consent
- •Group 2: Patients with Diabetes (n = 16)
- •Age 18-85 years
- •Diagnosis of diabetes
- •Echocardiogram within last 12 months showing no evidence of left ventricular hypertrophy or hemodynamic findings consistent with heart failure with preserved ejection fraction
- •Ability to provide informed consent
- •Group 3: Patients with Aortic Stenosis (n = 50)
- •Age 18-85 years
- •Echocardiogram or cardiac MRI scan within last 12 months documenting left ventricular hypertrophy and degenerative calcific aortic stenosis
- •Ability to provide informed consent
排除标准
- •Known contraindication to MRI
研究组 & 干预措施
Diabetes Patient Subjects
Patient subjects with diabetes will receive an IV injection of 11C-Martinostat and undergo simultaneous PET-MRI.
干预措施: PET-MRI (Device)
Healthy Subjects
Healthy subjects will receive an IV injection of 11C-Martinostat and undergo simultaneous PET-MRI.
干预措施: 11C-Martinostat (Drug)
Healthy Subjects
Healthy subjects will receive an IV injection of 11C-Martinostat and undergo simultaneous PET-MRI.
干预措施: PET-MRI (Device)
Diabetes Patient Subjects
Patient subjects with diabetes will receive an IV injection of 11C-Martinostat and undergo simultaneous PET-MRI.
干预措施: 11C-Martinostat (Drug)
Aortic Stenosis Patient Subjects
Patient subjects with aortic stenosis will receive an IV injection of 11C-Martinostat and undergo simultaneous PET-MRI before and after transcatheter valve replacement.
干预措施: 11C-Martinostat (Drug)
Aortic Stenosis Patient Subjects
Patient subjects with aortic stenosis will receive an IV injection of 11C-Martinostat and undergo simultaneous PET-MRI before and after transcatheter valve replacement.
干预措施: PET-MRI (Device)
结局指标
主要结局
11C-Martinostat Binding
时间窗: 10-60 minutes post-injection
Comparison of regional HDAC activity as measured by standard uptake value ratio (SUVR) of 11C-Martinostat between patient subjects with aortic stenosis or diabetes and healthy volunteers
次要结局
未报告次要终点
研究者
David E Sosnovik
Associate Professor of Medicine
Massachusetts General Hospital