NCT03008915

Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: Columbia University · Academic / Other
• Sex: All
• Age: 40 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Alpha-1 Antitrypsin Deficiency
• Emphysema
• Chronic Obstructive Pulmonary Disease

Interventions

Type	Name	Description
DRUG	Aspirin	81mg aspirin taken once per day in the morning
DRUG	Placebo	placebo taken once per day in the morning
OTHER	Withdrawal from alpha1 antitrypsin replacement therapy	After the completion of the randomization to aspirin and placebo, participants who are on alpha1 replacement therapy are asked to withhold their usual alpha1 antitrypsin replacement therapy for 5 weeks. This is not randomized.

Timeline

• Start date: 2017-01-01
• Primary completion: 2018-07-01
• Completion: 2020-10-01
• First posted: 2017-01-04
• Last updated: 2021-02-17
• Results posted: 2021-02-17

Locations

1 site across 1 country: United States