Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency

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

Secondary Outcome

 Endothelial apoptosis

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 Status

Drug

Estimated Enrollment

15

Start Date

January 2017

Completion Date

July 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

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 2020