Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency

NCT03008915 | Completed Phase 2 Results DMC

• 1 other identifier: AAAP9855
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

alpha-1 antitrypsin deficiency; Emphysema; chronic obstructive pulmonary disease

Outcome Measures

Primary Outcomes (1)

• Pulmonary Microvascular Blood Flow, Mean

  Pulmonary microvascular blood flow is measured on contrast-enhanced MRI, limited to blood flow in the 2cm periphery of the lung

  2 weeks

Secondary Outcomes (3)

• Endothelial Microparticles

  2 weeks

• Endothelial Microparticles

  5 weeks

• Pulmonary Microvascular Blood Flow, Mean

  5 weeks

Study Arms (2)

Aspirin first then placebo

ACTIVE COMPARATOR

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

Drug: Aspirin; Drug: Placebo; Other: Withdrawal from alpha1 antitrypsin replacement therapy

Placebo first then aspirin

PLACEBO COMPARATOR

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

Drug: Aspirin; Drug: Placebo; Other: Withdrawal from alpha1 antitrypsin replacement therapy

Interventions

Aspirin DRUG

81mg aspirin taken once per day in the morning

Aspirin first then placebo; Placebo first then aspirin

Placebo DRUG

placebo taken once per day in the morning

Aspirin first then placebo; Placebo first then aspirin

Withdrawal from alpha1 antitrypsin replacement therapy 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.

Aspirin first then placebo; Placebo first then aspirin

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Alpha-1 antitrypsin deficiency (PiZZ genotype)
• years of age or older
• Evidence of emphysema on CT scan as read by a Radiologist

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead
• Alpha-1 Foundation: collaborator
• Stony Wold-Herbert Fund, Inc.: collaborator

Study Sites (1)

Columbia University

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency; Emphysema; Pulmonary Disease, Chronic Obstructive

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Carrie Pistenmaa
• Organization: Columbia University

cp2346@"at"cumc.columbia.edu

212-342-4162

Study Officials

• Carrie Aaron, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: January 4, 2017
• Study Start: January 1, 2017
• Primary Completion: July 1, 2018
• Study Completion: October 1, 2020
• Last Updated: February 17, 2021
• Results First Posted: February 17, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)