Doxycycline for COPD in HIV-Infected Patients
Information source: Weill Medical College of Cornell University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV; Chronic Obstructive Pulmonary Disease (COPD); Emphysema
Intervention: Doxycycline (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Weill Medical College of Cornell University Official(s) and/or principal investigator(s): Robert Kaner, MD, Principal Investigator, Affiliation: Weill Cornell Medical College-New York Presbyterian Hospital Marshall Glesby, MD, Study Chair, Affiliation: Weill Cornell Medical College-New York Presbyterian Hospital
Overall contact: Charleen Hollmann, PhD, MPA, RN CCRP, Phone: 646-962-2672, Email: chollmann@med.cornell.edu
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.
Clinical Details
Official title: Doxycycline for COPD in HIV-Infected Patients
Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
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.
Detailed 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 85 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Documented HIV infection
2. Cluster of differentiation 4 (CD4) cell count >200 cells/mm3
3. HIV RNA < 400 copies/ml
4. Stable antiretroviral therapy for at least 12 weeks
5. Fulfills GOLD definition for COPD [post-bronchodilator with a forced expiratory
volume at one second and forced vital capacity ration (FEV1/FVC) < 0. 7] and/or has
radiographic evidence of emphysema
6. Current or history of smoking with minimum 3 pack-year history
7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 x
upper limit of normal
8. For women of childbearing potential: willingness to use 2 forms of birth control
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. International normalized ration (INR) > 1. 4
11. Platelets < 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
Locations and Contacts
Charleen Hollmann, PhD, MPA, RN CCRP, Phone: 646-962-2672, Email: chollmann@med.cornell.edu
Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York 10021, United States; Recruiting Marie Guevarra, MS, Phone: 646-962-4563, Email: mag3007@med.cornell.edu Aileen Orpilla, BE, Phone: 646-962-4564, Email: aio2001@med.cornell.edu Robert Kaner, MD, Principal Investigator Marshall Glesby, MD, Sub-Investigator Ronald Crystal, MD, Sub-Investigator Domenick Falcone, MD, Sub-Investigator Thomas Walsh, MD, Sub-Investigator Emilay Florez, BA, Sub-Investigator Sandra Hyde, BS, Sub-Investigator Odelya Pagovich, MD, Sub-Investigator Sarah O'Beirne, MD, Sub-Investigator Kirsis Ham, MSN, Sub-Investigator Lourdes Sanso, MD, Sub-Investigator
Additional Information
Starting date: January 2014
Last updated: April 19, 2015
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