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Doxycycline for COPD in HIV-Infected Patients

This study is currently recruiting participants.
Verified October 2016 by Robert J. Kaner, Weill Medical College of Cornell University
Sponsor:
ClinicalTrials.gov Identifier:
NCT01744093
First Posted: December 6, 2012
Last Update Posted: November 1, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Robert J. Kaner, Weill Medical College of Cornell University
November 20, 2012
December 6, 2012
November 1, 2016
January 2014
June 2017   (Final data collection date for primary outcome measure)
Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 2 years ]

To determine the safety and tolerability of twice daily doxycycline for 6 months in HIV-infected subjects with COPD and/or emphysema.

months in HIV-infected subjects with COPD and/or emphysema.

Safety and tolerability [ Time Frame: 2 years ]
To determine the safety, tolerability, and biologic effects of twice daily doxycycline for 6 months in HIV-infected subjects with COPD and/or emphysema.
Complete list of historical versions of study NCT01744093 on ClinicalTrials.gov Archive Site
Measure of physiologic and biologic effects based on levels of MMP activity in epithelial lining fluid before and after study drug administration. [ Time Frame: 2 years ]
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; change in FEV1.
Larger phase II clinical trial [ Time Frame: 2 years ]
To prepare and submit an application for a phase II clinical trial of doxycycline for COPD in HIV-infected subjects
Not Provided
Not Provided
 
Doxycycline for COPD in HIV-Infected Patients
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 is lead by a pulmonologist/researcher with expertise in HIV-associated COPD and an infectious diseases specialist/clinical trials expert.

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.
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
  • HIV
  • Chronic Obstructive Pulmonary Disease (COPD)
  • Emphysema
  • Drug: Doxycycline
    100 mg BID for six months
    Other Name: Vibramycin
  • Drug: Placebo (sugar pill)
    100 mg BID for six months
    Other Name: Placebo
  • Active Comparator: Doxycycline
    100 mg BID (orally) for 6 months
    Intervention: Drug: Doxycycline
  • Placebo Comparator: Placebo (sugar pill)
    100 mg BID (orally) for 6 months
    Intervention: Drug: Placebo (sugar pill)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
August 2017
June 2017   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 85 Years   (Adult, Senior)
No
Contact: Charleen Hollmann, PhD, MPA, RN 646-962-2672 chollmann@med.cornell.edu
Contact: Grace Mammen 646-962-4537 gwm2004@med.cornell.edu
United States
 
 
NCT01744093
1208012780
No
Not Provided
Plan to Share IPD: Undecided
Robert J. Kaner, Weill Medical College of Cornell University
Weill Medical College of Cornell University
Not Provided
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
Weill Medical College of Cornell University
October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP