Doxycycline for COPD in HIV-Infected Patients

Summary

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.

Conditions

• HIV
• Chronic Obstructive Pulmonary Disease (COPD)
• Emphysema

Interventions

DRUG

Doxycycline

100 mg twice daily (BID orally) x 24 weeks

DRUG

Placebo (sugar pill)

100 mg twice daily (BID orally) x 24 weeks

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Weill Medical College of Cornell University

  lead OTHER

Principal Investigators

• Robert Kaner, MD · Weill Cornell Medical College-New York Presbyterian Hospital

• Marshall Glesby, MD · Weill Cornell Medical College-New York Presbyterian Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-12-08

Primary Completion

2017-06-30

Completion

2020-12-30

Countries

• United States

Study Locations