Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency

NCT ID: NCT03008915

Last Updated: 2021-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2020-10-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Aspirin first then placebo

Aspirin 81mg for 2 weeks followed by a washout period and then placebo for 2 weeks

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

81mg aspirin taken once per day in the morning

Placebo

Intervention Type: DRUG

placebo taken once per day in the morning

Withdrawal from alpha1 antitrypsin replacement therapy

Intervention Type: OTHER

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.

Placebo first then aspirin

Placebo for 2 weeks followed by a washout period and then aspirin 81mg for 2 weeks

Group Type: PLACEBO_COMPARATOR

Aspirin

Intervention Type: DRUG

81mg aspirin taken once per day in the morning

Placebo

Intervention Type: DRUG

placebo taken once per day in the morning

Withdrawal from alpha1 antitrypsin replacement therapy

Intervention Type: OTHER

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.

Interventions

Aspirin

81mg aspirin taken once per day in the morning

Intervention Type: DRUG

Placebo

placebo taken once per day in the morning

Intervention Type: DRUG

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.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alpha-1 Foundation

OTHER

Sponsor Role: collaborator

Stony Wold-Herbert Fund, Inc.

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Carrie Aaron

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carrie Aaron, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AAAP9855

Identifier Type: -

Identifier Source: org_study_id