Clinical trial NCT03008915: Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency
Official title: Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alpha-1 Antitrypsin Deficiency
Emphysema
Chronic Obstructive Pulmonary Disease
Keywords: alpha-1 antitrypsin deficiency
Emphysema
chronic obstructive pulmonary disease
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Alpha-1 Foundation
name: Stony Wold-Herbert Fund, Inc.
First posted: 2017-01-04
Enrollment: 15
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Pulmonary Microvascular Blood Flow, Mean
timeFrame: 2 weeks
Secondary outcomes:
measure: Endothelial Microparticles
timeFrame: 2 weeks
measure: Endothelial Microparticles
timeFrame: 5 weeks
measure: Pulmonary Microvascular Blood Flow, Mean
timeFrame: 5 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University
state: New York
Study officials:
affiliation: Columbia University
name: Carrie Aaron, MD
role: PRINCIPAL_INVESTIGATOR
References: