HIV | Doxycycline for COPD in HIV-Infected Patients
HIV research study
What is the primary objective of this study?
In the context of improved survival from HIV infection itself, chronic obstructive pulmonary disease (COPD); a form of lung disease that includes emphysema, which makes breathing difficult) is emerging as an important cause of morbidity and perhaps ultimately mortality in this population. HIV-infected patients are at increased risk of chronic obstructive pulmonary disease, likely due to multiple factors, including an increased presence of smoking, chronic inflammation and progression of immunodeficiency, oxidant stress (excessive levels of natural chemicals called oxidants and free radicals that can damage tissue), and respiratory infections. While natural history data on COPD are limited in the era of potent antiretroviral therapy, earlier data suggest that the course of emphysema may be accelerated in this population. Our preliminary data suggest that several matrix metalloproteinases (MMPs) derived from alveolar macrophages (a type of immune cell found in the lungs) have an increased cellular response in HIV-infected smokers, which could contribute to accelerated emphysema. Matrix metalloproteinases are enzymes that break down the structural support of tissues, including the airways in the lung. Based on these observations, the investigators hypothesize that pharmacologic inhibition of matrix metalloproteinases by doxycycline will favorably modify the natural history of chronic obstructive pulmonary disease in HIV-infected patients. To test this hypothesis, the investigators propose conducting a proof of concept pilot study as a prelude to a possible phase II randomized, placebo-controlled trial (testing safety and efficacy in a larger population controlled with a \"sugar pill\") of doxycycline for COPD in HIV-infected patients should the proof of concept be successful. Our research team is lead by a pulmonologist/researcher with expertise in HIV-associated COPD and an infectious diseases specialist/clinical trials expert.
Who is eligible to participate?
Inclusion Criteria: 1. Documented HIV infection 2. CD4 cell count greater than 200 cells/mm3 3. HIV RNA less than 400 copies/ml 4. Stable antiretroviral therapy for greater than or equal to 12 weeks 5. Fulfills GOLD definition for COPD (post-bronchodilator FEV1/FVC less than 0.7) and/or has radiographic evidence of emphysema 6. Current or history of smoking with minimum 3 pack-year history 7. ALT and AST less than 3 x upper limit of normal 8. For women of childbearing potential: willingness to use 2 forms of birth control 9. Subjects on therapy for COPD must be on stable therapy for at least 4 weeks Exclusion Criteria: 1. Pulmonary infection, COPD exacerbation, or acute opportunistic infection within 30 days of entry 2. Conditions associated with increased sedation of bronchoscopy risk, including but not limited to Gold class 3 or 4 COPD, requirement for home oxygen, hypercapneic respiratory failure, poorly control hypertension 3. Known allergy/intolerance to doxycycline, atropine, or any local anesthetic 4. Inability to provide informed consent 5. Pregnant or lactating women 6. Men must agree not to attempt to make a woman pregnant of participate in sperm donation during the study and for 6 weeks after discontinuing the drug 7. Receipt of any investigational drug within 28 days 8. End stage renal disease 9. Cirrhosis 10. INR greater than 1.4 11. Platelets less than 80,000 12. Any condition including active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements or increase the risk of bronchoscopy
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Chronic Obstructive Pulmonary Disease (COPD)
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Doxycycline100 mg BID for six months
Drug:Placebo (sugar pill)100 mg BID for six months
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Doxycycline100 mg BID (orally) for 6 months
Placebo (sugar pill)100 mg BID (orally) for 6 months
Start Date: January 2014
Completed Date: August 2017
Primary Outcome: Number of participants with adverse events as a measure of safety and tolerability
Secondary Outcome: Measure of physiologic and biologic effects based on levels of MMP activity in epithelial lining fluid before and after study drug administration.
Study sponsors, principal investigator, and references
Principal Investigator: Robert Kaner, MD
Lead Sponsor: Weill Medical College of Cornell University