COPD, Emphysema, Emphysema or COPD
Conditions
Keywords
Platelet Dysfunction, Pulmonary Blood Vessel Injury, COPD, Emphysema
Brief summary
This is a 6 week crossover study in current and former smokers with and without COPD to evaluate whether 2 weeks of dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) improves pulmonary perfusion (i.e. blood flow in the lungs measured on a contrast CT scan) compared to placebo.
Detailed description
This is a single-center Phase IIa randomized double-blind crossover study in smokers with and without chronic obstructive pulmonary disease (COPD) to test whether dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) improves pulmonary perfusion (i.e. blood flow in the lungs) compared to placebo. We will enroll 30 subjects (20 with COPD, 10 without) who will each take part for 6 weeks. Participants and researchers will be blinded, they will not know which medications they are on first. Each participant will be asked to take aspirin and clopidogrel together for 2 weeks and also matching placebos for 2 weeks, with a 2 week washout period in between. Pulmonary blood flow will be evaluated with a contrast-enhanced CT scan of the chest two times over the 6 week study.
Interventions
COMBINATION_PRODUCTdual anti-platelet therapy
dual anti-platelet therapy
DRUGPlacebo
Placebo
Sponsors
Brigham and Women's Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All participants, investigators and care providers will be blinded as to dual-anti platelet therapy or placebo treatment
Intervention model description
Double-blind crossover study is a Phase 2 interventional study to assess whether dual-anti platelet therapy improves pulmonary blood flow compared to placebo
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
- COPD Cases: * COPD (FEV1/FVC \< 0.7, FVC \>= LLN), GOLD Stage I/II/III (FEV1 \>= 40%) * Current or former smoker of at least 10 pack years Inclusion Criteria - Controls: * Normal lung function (FEV1/FVC \>= 0.7, FEV1 and FVC \>= LLN) * Current or former smoker of at least 10 pack years
Exclusion criteria
* Platelet count \< 150,000/dL or self-report of a bleeding disorder; * Regular use of aspirin, clopidogrel or another antiplatelet medication; * Allergy to aspirin, clopidogrel, albuterol or iodine/IV contrast; * BMI \> 35; * History of intracranial hemorrhage, severe GI bleed or other life-threatening bleed; * Use of blood thinner (e.g. warfarin, lovenox or novel oral anti-coagulants); * Continuous use of supplemental oxygen at home; * Regular use of an NSAID; * Daily use of oral steroids, theophylline, roflumilast, or loop diuretics; * History of organ transplant or autoimmune disease on systemic therapy (rheumatoid arthritis, lupus); * Use of a biologic medication with regular injections; * Other current lung disease (interstitial lung disease, idiopathic pulmonary fibrosis, asthma); * IV drug use within the last year; * History of lung surgery to remove part of the lung; * Known bullae or advanced destructive emphysema in more than 1/3 of the lungs; * Treatment for cancer (systemic therapy or surgical/radiation within the thorax) in the last 12 months; * Known diagnosis of pulmonary hypertension; * Known systolic heart failure (RV or LV EF \< 40%); * Acute or chronic renal insufficiency (estimated glomerular filtration rate \[GFR\] \<60 mL/min/1.73 m2 or self-report). GFR will be calculated using the CKD-EPI equation; * Current or planned pregnancy in the next year; * Regular marijuana smoking; * Exacerbation of respiratory symptoms within the previous 6 weeks, such as that requiring hospitalization, oral prednisone or antibiotics to control symptoms, or longer and not yet returned to baseline; and * Chest, abdominal or eye surgery, or a heart attack or stroke, within the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Microvascular Blood Volume, CV | After 2 weeks of therapy | Coefficient of variation (CV) of pulmonary microvascular blood volume on dual energy CT scan, comparing on dual antiplatelet therapy to placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Microvascular Blood Volume | After 2 weeks of therapy | Pulmonary microvascular blood volume on dual energy CT scan, comparing on dual antiplatelet therapy to placebo |
| Oxygen Saturation | After 2 weeks of therapy | Resting oxygen saturation |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORCarrie L Pistenmaa, MD, MS
Brigham and Women's Hospital
Participant flow
Recruitment details
15
Pre-assignment details
10 COPD cases, 5 controls
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 69.0 years STANDARD_DEVIATION 2.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| ppFEV1 | 109.8 % STANDARD_DEVIATION 8.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 4 | 0 / 5 |
| other Total, other adverse events | 5 / 10 | 2 / 10 | 2 / 4 | 0 / 5 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 4 | 0 / 5 |
Outcome results
None listed