Doxycycline for COPD in HIV-Infected Patients

NCT01744093 | Completed Results

• 2 other identifiers: 1208012780R34HL117352
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

HIV; COPD; Chronic Obstructive Pulmonary Disease; Emphysema

Outcome Measures

Primary Outcomes (2)

• Safety of Doxycycline, as Measured by the Number of Subjects With Any Treatment-related Adverse Events.

  To determine the safety of twice daily doxycycline for 24 weeks in HIV-infected subjects with COPD and/or emphysema as measured by the number of subjects with any treatment-related adverse events.

  Up to 24 weeks

• Tolerability of Doxycycline, as Measured by the Number of Subjects With a Dose-limiting Toxicity

  To determine the tolerability of twice daily doxycycline for 24 weeks in HIV-infected subjects with COPD and/or emphysema as measured by those subjects experiencing a dose-limiting toxicity

  Up to 24 weeks

Secondary Outcomes (4)

• Clinical: Change in Pulmonary Function (FEV1)

  24 Weeks

• Percent Change in BAL MMP-9 Activity

  12 Weeks

• Doxycycline Levels

  12 Weeks

• Doxycycline Levels in BAL

  12 Week

Study Arms (2)

Doxycycline

ACTIVE COMPARATOR

100 mg twice daily (BID orally) x 24 weeks

Drug: Doxycycline

Placebo (sugar pill)

PLACEBO COMPARATOR

100 mg twice daily (BID orally) x 24 weeks

Drug: Placebo (sugar pill)

Interventions

Doxycycline DRUG

100 mg twice daily (BID orally) x 24 weeks

Also known as: Vibramycin

Doxycycline

Placebo (sugar pill) DRUG

100 mg twice daily (BID orally) x 24 weeks

Also known as: Placebo

Placebo (sugar pill)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented HIV infection
• CD4 cell count greater than 200 cells/mm3
• HIV RNA less than 400 copies/ml
• Stable antiretroviral therapy for greater than or equal to 12 weeks
• Fulfills GOLD definition for COPD (post-bronchodilator FEV1/FVC less than 0.7) and/or has radiographic evidence of emphysema
• Current or history of smoking with minimum 3 pack-year history
• ALT and AST less than 3 x upper limit of normal
• For women of childbearing potential: willingness to use 2 forms of birth control
• Subjects on therapy for COPD must be on stable therapy for at least 4 weeks

You may not qualify if:

• Pulmonary infection, COPD exacerbation, or acute opportunistic infection within 30 days of entry
• 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 controlled hypertension
• Known allergy/intolerance to doxycycline, atropine, or any local anesthetic
• Inability to provide informed consent
• Pregnant or lactating women
• Men must agree not to attempt to make a woman pregnant or participate in sperm donation during the study and for 6 weeks after discontinuing the drug
• End stage renal disease
• Cirrhosis
• INR greater than 1.4
• Platelets less than 80,000
• 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
• Active or planned participation in any other clinical trial or observational study without prior approval from the PI

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Genetic Medicine

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Emphysema

Interventions

Doxycycline; Sugars

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Carbohydrates

Results Point of Contact

• Title: Mei Wang, BS, CCRP
• Organization: Weill Cornell Medicine

mew2001@med.cornell.edu

646-962-2672

Study Officials

• Robert Kaner, MD

  Weill Cornell Medical College-New York Presbyterian Hospital

  PRINCIPAL INVESTIGATOR

• Marshall Glesby, MD

  Weill Cornell Medical College-New York Presbyterian Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2012
• First Posted: December 6, 2012
• Study Start: December 8, 2014
• Primary Completion: June 30, 2017
• Study Completion: December 30, 2020
• Last Updated: July 21, 2022
• Results First Posted: October 10, 2018

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)