Anti-Platelets in Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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This is a 6 week crossover study in 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
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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.

Official Title
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Dual Anti-platelet Therapy in Chronic Obstructive Pulmonary Disease Study

Conditions
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COPD, Emphysema, Emphysema or COPD

Intervention / Treatment
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* Combination Product: dual anti-platelet therapy
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria - COPD Cases: COPD (FEV1/FVC < 0.7, FVC >= 80%), GOLD Stage I/II (FEV1 >= 50%) Evidence of visual emphysema (centrilobular emphysema or panlobular emphysema) on prior CT scan Former smoker at least 10 pack years Inclusion Criteria - Controls: Normal lung function (FEV1/FVC > 0.7, FEV1 and FVC >= 80%) No evidence of visual emphysema on prior CT scan Former smoker 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 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); Use of supplemental oxygen at home, other than only nocturnal use; Regular use of an NSAID; Daily use of oral steroids, theophylline, roflumilast, or diuretics; History of organ transplant or autoimmune disease (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; Chest CT scan within 5 years showing significant lung mass, infiltrate (ground glass or other consolidation), or scarring/fibrosis of the lungs; Bullae or advanced destructive emphysema in more than 1/3 of the lungs; Treatment for cancer within the last 12 months; Known diagnosis of pulmonary hypertension; Known systolic heart failure (RV or LV EF < 40%); Use of medications for diabetes (metformin, januvia, insulin, etc); 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; Allergy to iodine contrast; Use of tobacco products (cigarettes, cigars or pipes) or E-cigarettes within 1 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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COPD Cases: Dual antiplatelet therapy first, then placebo<br>Dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) will be given for 2 weeks, followed by 2 weeks without intervention, then 2 weeks of placebo | Combination Product: dual anti-platelet therapy<br>* dual anti-platelet therapy<br>* Other names: clopidogrel 75mg tab;Drug: Placebo<br>* Placebo<br>|
| Placebo Comparator: COPD Cases: Placebo first, then dual antiplatelet therapy<br>Placebos for each therapy (2 pills) will be given for 2 weeks, followed by 2 weeks without intervention, then 2 weeks of dual antiplatelet therapy | Combination Product: dual anti-platelet therapy<br>* dual anti-platelet therapy<br>* Other names: clopidogrel 75mg tab;Drug: Placebo<br>* Placebo<br>|
| Active Comparator: Controls: Dual antiplatelet therapy first, then placebo<br>Dual antiplatelet therapy (aspirin 81mg and clopidogrel 75mg) will be given for 2 weeks, followed by 2 weeks without intervention, then 2 weeks of placebo | Combination Product: dual anti-platelet therapy<br>* dual anti-platelet therapy<br>* Other names: clopidogrel 75mg tab;Drug: Placebo<br>* Placebo<br>|
| Placebo Comparator: Controls: Placebo first, then dual antiplatelet therapy<br>Placebos for each therapy (2 pills) will be given for 2 weeks, followed by 2 weeks without intervention, then 2 weeks of dual antiplatelet therapy | Combination Product: dual anti-platelet therapy<br>* dual anti-platelet therapy<br>* Other names: clopidogrel 75mg tab;Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary microvascular blood volume, CV | Coefficient of variation (CV) of pulmonary microvascular blood volume on dual energy CT scan, comparing on dual antiplatelet therapy to placebo | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary microvascular blood volume | Pulmonary microvascular blood volume on dual energy CT scan, comparing on dual antiplatelet therapy to placebo | 6 weeks | 
| Pulmonary microvascular blood flow, CV | Coefficient of variation (CV) of pulmonary microvascular blood flow on dual energy CT scan, comparing on dual antiplatelet therapy to placebo | 6 weeks | 
| Pulmonary microvascular blood flow | Pulmonary microvascular blood flow on dual energy CT scan, comparing on dual antiplatelet therapy to placebo | 6 weeks | 
| Diffusing capacity | DLCO | 6 weeks | 
| Oxygen saturation | Resting oxygen saturation | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platelet Dysfunction, Pulmonary Blood Vessel Injury, COPD, Emphysema