Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Pulmonary Microvascular Blood Flow, Mean
研究概览
简要总结
The aim of this study is to test whether aspirin improves endothelial function in alpha-1 antitrypsin deficiency-associated lung disease, measured by pulmonary microvascular blood flow on magnetic resonance imaging (MRI) and with apoptotic endothelial microparticles.
详细描述
Emphysema is a common type of lung disease in patients with alpha-1 antitrypsin deficiency (AATD). Emphysema refers to destruction of the fine network of air spaces and blood vessels in the lung, and results in what looks like "holes" in the lung. Emphysema is associated with an increased risk of death but currently no medications, except for replacement of alpha-1 antitrypsin (AAT), have been shown to treat emphysema.
The study plans to enroll subjects with alpha-1 antitrypsin deficiency-associated lung disease (PiZZ phenotype) to perform a cross-over randomized controlled trial (RCT) of aspirin compared to placebo to test the hypotheses that aspirin is effective in improving blood flow in the lungs and reducing damage to the endothelial cells. Subjects will be randomized to receive aspirin or placebo for 2 weeks. There will be a 2-week washout period, then the participant will be crossed over to receive the other treatment (those who received aspirin first will receive the placebo and those who received the placebo first will receive aspirin).
Participants who are on alpha-1 replacement therapy who have had fewer than 2 exacerbations in the last year will be asked whether they are interested in a withdrawal study. For this second part of the study, eligible and willing participants will be asked to stop their alpha-1 replacement therapy for 5 weeks and come in for a 4th study visit. This will allow AAT levels to drop briefly to those seen in the absence of AAT augmentation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Alpha-1 antitrypsin deficiency (PiZZ genotype)
- •40 years of age or older
- •Evidence of emphysema on CT scan as read by a Radiologist
排除标准
- •Platelet count < 150,000/dL, history of intracranial hemorrhage or severe GI bleed, use of systemic anticoagulant, physician prescribed use of antiplatelet drug (including aspirin and P2Y12 receptor inhibitors), or known severe liver disease
- •Immunosuppression by use of medications (including oral prednisone), or those with immunomodulatory disease (organ transplantation, autoimmune conditions or actively-treated malignancy)
- •Known atrial fibrillation or left ventricular (LV) systolic heart failure
- •Contraindication to MRI, including pregnancy, weight > 300 lbs (due to weight limits of the machine), those with pacemakers, aneurysm clips, cochlear implants or other implanted electronic devices, or severe claustrophobia;
- •Chronic renal insufficiency (estimated GFR < 45 L/min/1.73 m2 or self report) due to slightly increased risk of nephrogenic systemic fibrosis from gadolinium administration and aspirin-related renal insufficiency
- •Exacerbation of respiratory symptoms within the previous 6 weeks, such as that requiring hospitalization, oral prednisone or antibiotics to control symptoms.
研究组 & 干预措施
Aspirin first then placebo
Aspirin 81mg for 2 weeks followed by a washout period and then placebo for 2 weeks
干预措施: Withdrawal from alpha1 antitrypsin replacement therapy (Other)
Aspirin first then placebo
Aspirin 81mg for 2 weeks followed by a washout period and then placebo for 2 weeks
干预措施: Aspirin (Drug)
Aspirin first then placebo
Aspirin 81mg for 2 weeks followed by a washout period and then placebo for 2 weeks
干预措施: Placebo (Drug)
Placebo first then aspirin
Placebo for 2 weeks followed by a washout period and then aspirin 81mg for 2 weeks
干预措施: Aspirin (Drug)
Placebo first then aspirin
Placebo for 2 weeks followed by a washout period and then aspirin 81mg for 2 weeks
干预措施: Placebo (Drug)
Placebo first then aspirin
Placebo for 2 weeks followed by a washout period and then aspirin 81mg for 2 weeks
干预措施: Withdrawal from alpha1 antitrypsin replacement therapy (Other)
结局指标
主要结局
Pulmonary Microvascular Blood Flow, Mean
时间窗: 2 weeks
Pulmonary microvascular blood flow is measured on contrast-enhanced MRI, limited to blood flow in the 2cm periphery of the lung
次要结局
- Endothelial Microparticles(5 weeks)
- Pulmonary Microvascular Blood Flow, Mean(5 weeks)
研究者
Carrie Aaron
Assistant Professor of Medicine
Columbia University