Alpha-1 Antitrypsin DeficiencyPhase 2NCT03008915
Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency
A Phase 2 study testing Aspirin and Withdrawal from alpha1 antitrypsin replacement therapy in people with Alpha-1 Antitrypsin Deficiency and Emphysema, run by Columbia University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Alpha-1 Antitrypsin Deficiency, Emphysema, Chronic Obstructive Pulmonary Disease
- What is being tested?
- Aspirin and Withdrawal from alpha1 antitrypsin replacement therapy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to Oct 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Alpha-1 antitrypsin deficiency (PiZZ genotype)
- 40 years of age or older
- Evidence of emphysema on CT scan as read by a Radiologist
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Being tested
- Aspirin, Placebo, Withdrawal from alpha1 antitrypsin replacement therapy
- Keywords
- alpha-1 antitrypsin deficiency, Emphysema, chronic obstructive pulmonary disease
- Medical subject headings
- alpha 1-Antitrypsin Deficiency, Emphysema, Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
81mg aspirin taken once per day in the morning
PlaceboDrug
placebo taken once per day in the morning
Withdrawal from alpha1 antitrypsin replacement therapyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Aspirin first then placebo | Active comparator | Aspirin 81mg for 2 weeks followed by a washout period and then placebo for 2 weeks Receives: 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 Receives: Drug: Aspirin; Drug: Placebo; Other: Withdrawal from alpha1 antitrypsin replacement therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 weeks
Secondary outcomes (3)
Endothelial Microparticles
Endothelial microparticles (EMPs) are vesicles shed from endothelial plasma membranes into the circulation in response to endothelial cell perturbation. CD31+ is a measure of apoptotic endothelial microparticles, CD62+ (P-selectin) is a measure of endothelial activation, and Annexin V/CD31+ is a more specific marker of endothelial cell apoptosis.
Measured: 2 weeks
Endothelial Microparticles
Endothelial microparticles (EMPs) are vesicles shed from endothelial plasma membranes into the circulation in response to endothelial cell perturbation. CD31+ is a measure of apoptotic endothelial microparticles, CD62+ (P-selectin) is a measure of endothelial activation, and Annexin V/CD31+ is a more specific marker of endothelial cell apoptosis.
Measured: 5 weeks
Pulmonary Microvascular Blood Flow, Mean
Pulmonary microvascular blood flow is measured on contrast-enhanced MRI in the peripheral 2cm of the lung.
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionJul 2018
- Study completionOct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alpha-1 Antitrypsin DeficiencyStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Alpha-1 Foundation, Stony Wold-Herbert Fund, Inc.
- Responsible party
- Principal investigator, Carrie Aaron, Columbia University
- Investigators
- Carrie Aaron, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03008915
- Sponsor's protocol ID
- AAAP9855
- Status last verified
- Jan 2021
- First submitted
- 22 Dec 2016
- Last updated
- 17 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency
- ClinicalTrials.gov ID
- NCT03008915
- Acronym / sponsor ID
- AAAP9855
- Keywords
- alpha-1 antitrypsin deficiency, Emphysema, chronic obstructive pulmonary disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Alpha-1 Foundation, Stony Wold-Herbert Fund, Inc.
- Study start
- Jan 2017 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- Oct 2020 (actual)
- First posted
- 4 Jan 2017 (estimated)
- Results
- Posted 17 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aspirin first then placebo | Active comparator | Drug: Aspirin, Drug: Placebo, Other: Withdrawal from alpha1 antitrypsin replacement therapyAspirin 81mg for 2 weeks followed by a washout period and then placebo for 2 weeks |
| Placebo first then aspirin | Placebo comparator | Drug: Aspirin, Drug: Placebo, Other: Withdrawal from alpha1 antitrypsin replacement therapyPlacebo for 2 weeks followed by a washout period and then aspirin 81mg for 2 weeks |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Alpha-1 antitrypsin deficiency (PiZZ genotype)
- 40 years of age or older
- Evidence of emphysema on CT scan as read by a Radiologist
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aspirin81mg aspirin taken once per day in the morning | Drug | Aspirin first then placebo, Placebo first then aspirin |
| Placeboplacebo taken once per day in the morning | Drug | Aspirin first then placebo, Placebo first then aspirin |
| Withdrawal from alpha1 antitrypsin replacement therapyAfter 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. | Other | Aspirin first then placebo, Placebo first then aspirin |
Primary outcome
Pulmonary Microvascular Blood Flow, Mean
Time frame: 2 weeks
Pulmonary microvascular blood flow is measured on contrast-enhanced MRI, limited to blood flow in the 2cm periphery of the lung
3 secondary outcomes
Endothelial Microparticles
Time frame: 2 weeks
Endothelial Microparticles
Time frame: 5 weeks
Pulmonary Microvascular Blood Flow, Mean
Time frame: 5 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carrie Aaron, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aspirin and Withdrawal from alpha1 antitrypsin replacement therapy in people with Alpha-1 Antitrypsin Deficiency and Emphysema, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pulmonary Microvascular Blood Flow, Mean (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2021; AzTrials last refreshed its copy on 31 Oct 2026.