Doxycycline for COPD in HIV-Infected Patients
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, led by a pulmonologist/researcher with expertise in HIV-associated COPD and an infectious diseases specialist/clinical trials expert, is well positioned to propose such a trial to the NIH-funded AIDS Clinical Trials Group (ACTG).
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Doxycycline for COPD in HIV-Infected Patients|
- Safety and tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]To determine the safety, tolerability, and biologic effects of twice daily doxycycline for 6 months in HIV-infected subjects with COPD and/or emphysema.
- Larger phase II clinical trial [ Time Frame: 2 years ] [ Designated as safety issue: No ]To prepare and submit an application for a phase II clinical trial of doxycycline for COPD in HIV-infected subjects
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Doxycycline
100 mg BID (orally) for 6 months
100 mg BID for six months
Other Name: Vibramycin
Placebo Comparator: Placebo (sugar pill)
100 mg BID for 6 months
Chronic obstructive pulmonary disease (COPD) is emerging as an important cause of morbidity in HIV-infected patients, likely due to multiple factors, including an increased prevalence of smoking, chronic inflammation and immune activation, oxidant stress and respiratory infections. Our preliminary data suggest that several lung matrix metalloproteinases (MMPs) are upregulated in HIV-infected smokers, which could contribute to accelerated emphysema by virtue of their ability to degrade extracellular matrix and basement membrane components. Our aims are: (1) end, we first propose to conduct a pilot study to enable us to address the following Specific aims: Aim 1. To determine the safety, tolerability, and biologic effects of twice daily doxycycline for 6 months in HIV-infected subjects with COPD; and (2) to prepare and submit an application for a phase II clinical trial of doxycycline for COPD in HIV-infected subjects. To address the first aim, we will conduct a randomized, double-blind, placebo-controlled pilot study of doxycycline 100 mg twice daily in 30 HIV-infected subjects with COPD(2:1 doxy:placebo). The primary endpoint will be safety/tolerability and secondary endpoints will include change in FEV1, reduction of MMP activity in epithelial lining fluid and cells obtained by bronchoscopy and doxycycline levels in blood, ELF and bronchoalveolar lavage (BAL) cell pellets. In addition to providing novel insights into the biologic effects of doxycycline in the lung, the pilot study will inform selection of endpoints for a phase II trial, which ultimately will address an unmet medical need for novel interventions for COPD/emphysema in HIV-infected patients.
|Contact: Charleen Hollmann, RN, PhD||646-962-2672||CORA@med.cornell.edu|
|United States, New York|
|Weill Cornell Medical College-New York Presbyterian Hospital||Not yet recruiting|
|New York, New York, United States, 10021|
|Contact: Charleen Hollmann, RN, PhD 646-962-2672 CORA@med.cornell.edu|
|Principal Investigator: Robert Kaner, MD|
|Sub-Investigator: Marshall Glesby, MD|
|Sub-Investigator: Ronald Crystal, MD|
|Sub-Investigator: Domenick Falcone, MD|
|Sub-Investigator: Thomas Walsh, MD|
|Principal Investigator:||Robert Kaner, MD||Weill Cornell Medical College-New York Presbyterian Hospital|
|Study Chair:||Marshall Glesby, MD||Weill Cornell Medical College-New York Presbyterian Hospital|