Brief Title
Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency
Official Title
Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency
Brief Summary
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.
Detailed Description
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Pulmonary Microvascular Blood Flow, Mean
Secondary Outcome
Endothelial Microparticles
Condition
Alpha-1 Antitrypsin Deficiency
Intervention
Aspirin
Study Arms / Comparison Groups
Aspirin first then placebo
Description: Aspirin 81mg for 2 weeks followed by a washout period and then placebo for 2 weeks
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
15
Start Date
January 2017
Completion Date
October 2020
Primary Completion Date
July 2018
Eligibility Criteria
Inclusion Criteria: - Alpha-1 antitrypsin deficiency (PiZZ genotype) - 40 years of age or older - Evidence of emphysema on CT scan as read by a Radiologist Exclusion Criteria: - 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.
Gender
All
Ages
40 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Carrie Aaron, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03008915
Organization ID
AAAP9855
Responsible Party
Principal Investigator
Study Sponsor
Columbia University
Collaborators
Alpha-1 Foundation
Study Sponsor
Carrie Aaron, MD, Principal Investigator, Columbia University
Verification Date
January 2021