Vasculopathy and Remodeling of Coronary Arteries in FRDA Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 2
- 主要终点
- vasomotor tone
研究概览
简要总结
Friedreich's ataxia is a debilitating, inherited disease cause by mutations in a protein called frataxin (FXN). FXN is one of several proteins that controls the production of iron-sulfur clusters, molecules that are essential for energy production in our cells as well as repair of our genetic code embedded in DNA molecules. Friedreich's ataxia (FRDA) and deficiency of FXN results in a nerve disease affecting coordination and a condition called hypertrophic cardiomyopathy (HCM), marked by an abnormal thickening of the heart. Patients with HCM can then develop pulmonary hypertension (PH), a deadly condition of the blood vessels of the lung. While most of the research in FRDA has focused on nerves and heart muscle, alterations in blood vessels of the heart and lung may worsen disease in FRDA. But, the role of FXN in these blood vessels has never been defined.
Investigators pilot data suggest that Frataxin (FXN ) deficiency can control senescence and downstream function in various types of Endothelial cells (ECs), investigators hypothesize that Friedreich's Ataxia (FRDA) patients may demonstrate endothelial cells EC abnormalities throughout the vasculature potentially before overt cardiomyopathy develops.
详细描述
Procedure in details:
Investigators have extensive experience in the performance of forearm blood flow studies using strain gauge plethysmography in patient volunteers. Endothelial dysfunction will be tested according to methodologies employed in our blood flow laboratories for more than a decade. Strain-gauge plethysmography is used to measure forearm blood flow during infusions of acetylcholine [ACh], and sodium nitroprusside [SNP] . Intra-arterial infusions of acetylcholine to test endothelium-dependent blood flow. Acetylcholine acts on muscarinic receptors to increase intracellular calcium levels and activate endothelial nitic oxide (NO) synthase. SNP is an exogenous source of NO, to assess endothelium-independent vasodilatation.
Cumulative dose response curves will be constructed over 5-minute incremental infusions. Study doctor will proceed in the following order:
- SNP 0.8 1.6 and 3.2 mcg/min
- ACh 7.5 15 and 30 mcg/min
- Normal saline
Forearm blood flow (FBF) measurements in both arms will be made using venous occlusion strain-gauge plethysmography prior to the initiation of any intra-arterial infusions. Blood pressure and heart rate will be measured during the procedure through the ECG. All FBF measurements will be expressed as mL/min per 100-1 mL forearm volume according to prior studies and the Whitney method.1, 2 Resting baseline FBF will be measured at least 30 minutes after venous and arterial catheter placement to ensure that blood flows in the cannulated arms are stabilized. Study team will measure FBF during the last 2 minutes of each infusion period. Infusions of individual vasoactive medications will occur over a 15-minute interval. There will be a 25-minute washout between vasoactive medications. The ACh 30 mcg/min will run for a total of 10 minutes.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients older than 18
- •Has recent clinical echocardiography data confirming normal cardiac function
排除标准
- •Patients younger than 18
- •Has abnormal cardiac function
结局指标
主要结局
vasomotor tone
时间窗: 2-4 hours
We will quantify vasomotor tone in regard to level of vasoconstriction and vasodilation at rest and in response to pharmacologic stimulation
次要结局
未报告次要终点
研究者
Stephen Y. Chan
Professor of Medicine
University of Pittsburgh