HIVNCT01744093
Doxycycline for COPD in HIV-Infected Patients
A study testing Doxycycline in people with HIV and Chronic Obstructive Pulmonary Disease (COPD), run by Weill Medical College of Cornell University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- HIV, Chronic Obstructive Pulmonary Disease (COPD), Emphysema
- What is being tested?
- Doxycycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Dec 2014to 30 Dec 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- HIV, Chronic Obstructive Pulmonary Disease (COPD), Emphysema
- Being tested
- Doxycycline, Placebo (sugar pill)
- Keywords
- HIV, COPD, Chronic Obstructive Pulmonary Disease, Emphysema
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Emphysema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
Also called Vibramycin
100 mg twice daily (BID orally) x 24 weeks
Placebo (sugar pill)Drug
Also called Placebo
100 mg twice daily (BID orally) x 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline | Active comparator | 100 mg twice daily (BID orally) x 24 weeks Receives: Drug: Doxycycline |
| Placebo (sugar pill) | Placebo comparator | 100 mg twice daily (BID orally) x 24 weeks Receives: Drug: Placebo (sugar pill) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: Up to 24 weeks
Secondary outcomes (4)
Clinical: Change in Pulmonary Function (FEV1)
FEV1 is the volume of air exhaled during the first second of a forced expiratory maneuver.
Measured: 24 Weeks
Percent Change in BAL MMP-9 Activity
Percent change of MMP-9 activity in bronchoalveolar lavage (BAL) fluid.
Measured: 12 Weeks
Doxycycline Levels
Doxycycline level in serum
Measured: 12 Weeks
Doxycycline Levels in BAL
Doxycycline levels in bronchoalveolar lavage (BAL) fluid.
Measured: 12 Week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2012 (estimated)
- Study start8 Dec 2014
- Primary completion30 Jun 2017
- Study completion30 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Robert Kaner, MD, Principal investigator, Weill Cornell Medical College-New York Presbyterian HospitalMarshall Glesby, MD, Principal investigator, Weill Cornell Medical College-New York Presbyterian Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01744093
- Sponsor's protocol ID
- 1208012780
- Other IDs
- R34HL117352
- Status last verified
- Jul 2022
- First submitted
- 20 Nov 2012
- Last updated
- 21 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Kaner RJ, O'Beirne SL, Krambrink A, Spino C, Yang HS, Zhu YS, Crystal RG, Glesby MJ. Randomized Double-Blinded Pilot Study of Doxycycline for HIV-Associated COPD and Emphysema. Chronic Obstr Pulm Dis. 2026 Sep 30. doi: 10.15326/jcopdf.2026.0796. Online ahead of print.
PubMed 42852919
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Doxycycline for COPD in HIV-Infected Patients
- ClinicalTrials.gov ID
- NCT01744093
- Acronym / sponsor ID
- 1208012780
- Conditions
- HIV, Chronic Obstructive Pulmonary Disease (COPD), Emphysema
- Keywords
- HIV, COPD, Chronic Obstructive Pulmonary Disease, Emphysema
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 8 Dec 2014 (actual)
- Primary completion
- 30 Jun 2017 (actual)
- Study completion
- 30 Dec 2020 (actual)
- First posted
- 6 Dec 2012 (estimated)
- Results
- Posted 10 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Doxycycline | Active comparator | Drug: Doxycycline100 mg twice daily (BID orally) x 24 weeks |
| Placebo (sugar pill) | Placebo comparator | Drug: Placebo (sugar pill)100 mg twice daily (BID orally) x 24 weeks |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DoxycyclineAlso: Vibramycin100 mg twice daily (BID orally) x 24 weeks | Drug | Doxycycline |
| Placebo (sugar pill)Also: Placebo100 mg twice daily (BID orally) x 24 weeks | Drug | Placebo (sugar pill) |
Primary outcome
Safety of Doxycycline, as Measured by the Number of Subjects With Any Treatment-related Adverse Events.
Time frame: Up to 24 weeks
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.
Tolerability of Doxycycline, as Measured by the Number of Subjects With a Dose-limiting Toxicity
Time frame: Up to 24 weeks
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
4 secondary outcomes
Clinical: Change in Pulmonary Function (FEV1)
Time frame: 24 Weeks
Percent Change in BAL MMP-9 Activity
Time frame: 12 Weeks
Doxycycline Levels
Time frame: 12 Weeks
Doxycycline Levels in BAL
Time frame: 12 Week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42852919Kaner RJ, O'Beirne SL, Krambrink A, Spino C, Yang HS, Zhu YS, Crystal RG, Glesby MJ. Randomized Double-Blinded Pilot Study of Doxycycline for HIV-Associated COPD and Emphysema. Chronic Obstr Pulm Dis. 2026 Sep 30. doi: 10.15326/jcopdf.2026.0796. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Kaner, MD principal investigator
Weill Cornell Medical College-New York Presbyterian Hospital
Marshall Glesby, MD principal investigator
Weill Cornell Medical College-New York Presbyterian Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Doxycycline in people with HIV and Chronic Obstructive Pulmonary Disease (COPD), run by Weill Medical College of Cornell University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Doxycycline, as Measured by the Number of Subjects With Any Treatment-related Adverse Events. (time frame: Up to 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01744093, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2022.