Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT01744093 |
Other study ID # |
1208012780 |
Secondary ID |
R34HL117352 |
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
December 8, 2014 |
Est. completion date |
December 30, 2020 |
Study information
Verified date |
July 2022 |
Source |
Weill Medical College of Cornell University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
Description:
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
Specific Aim is to determine the safety, tolerability, and biologic effects of twice daily
doxycycline for 6 months in HIV-infected subjects with COPD. To address this 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.