Doxycycline for Emphysema in People Living With HIV (The DEPTH Trial)

NCT ID: NCT05382208

Last Updated: 2026-01-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-22
• Study Completion Date: 2027-02-28

Brief Summary

The purpose of this study is to determine if doxycycline will reduce progression of emphysema in people living with HIV.

The secondary objectives are to examine the effects of doxycycline on change in quantity of emphysema, six minute walk distance, patient reported outcomes, ratio of forced expiratory volume in 1 second and forced vital capacity. Secondary objectives will also describe the safety and tolerability of doxycycline and determine if doxycycline is associated with development of antibiotic-resistant bacterial infections.

Detailed Description

This study is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial in approximately 250 people living with HIV who have emphysema.

Eligible participants will be randomized in a 1:1 fashion to doxycycline or placebo. Participants will receive 100 mg doxycycline orally or matched placebo twice a day for 72 weeks.

Conditions

Emphysema; HIV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Doxycycline

Doxycycline 100mg orally twice a day

Group Type: EXPERIMENTAL

Doxycycline

Intervention Type: DRUG

Doxycycline 100 mg orally twice a day.

Placebo

Matching placebo orally twice a day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo orally twice a day.

Interventions

Doxycycline

Doxycycline 100 mg orally twice a day.

Intervention Type: DRUG

Placebo

Matching placebo orally twice a day.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female age 30 years and older at screening visit.
• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to the enrollment visit, and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
• Current or former smoker with at least a 3 pack-year history of cigarette smoking at screening visit.
• Evidence of emphysema on high resolution CT (HRCT) of the chest done at pre-entry visit (Visit 2). Emphysema is defined as either:

1. Mild, moderate, or severe emphysema assessed by central reader(s) at the CT Imaging Core; or

2. Quantification of ≥ 5% of voxels with density < -950 Hounsfield Units (HU) as quantified by the CT Imaging Core.

All participants with emphysema by either or both criteria must have ≤ 35% of voxels with density < -950 HU.

• Screening and Entry DLCO measurements must be within 15% of each other. The PFT quality at both visits must be acceptable based on ATS Quality Criteria.

1. Screening (Visit 1) Pulmonary Function Test meets ATS quality criteria as determined by a central reviewer at the PFT Reading Core (UCLA)

2. Baseline (Visit 2) Pulmonary Function Test meets ATS quality criteria as determined by the central reviewer at the PFT Reading Core (UCLA), Site Investigator, or DEPTH Trial Leadership.

• HIV-1 RNA level < 200 copies/ml within 90 days prior to the Entry/Baseline visit by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
• CD4 cell count > 100 cells/mm3 within 90 days prior to the Entry/Baseline visit.by any US laboratory that has a CLIA certification or its equivalent.
• Stable antiretroviral therapy for greater than or equal to 8 weeks prior to the Entry/Baseline visit. Substitutions of one formulation of a drug for another are not considered changes in antiretroviral therapy for the purpose of defining stable therapy..
• Serum ALT and AST < 3 x upper limit of normal within 60 days prior to the Entry/Baseline visit.
• Participants on therapy for COPD must be on stable therapy for at least 4 weeks prior to the Entry/Baseline visit.
• Documentation of serum alpha-1-antitrypsin level above the lower limit of normal from a test done at any time prior to the Entry/Baseline visit.
• Provision of signed and dated written informed consent.
• Stated willingness to adhere to all study procedures and anticipated availability for the duration of the study.
• Life expectancy > 2 years in the opinion of the site investigator.
• Ability to take oral medication and willingness to adhere to the study drug.
• For individuals of reproductive potential, negative serum or urine pregnancy test with a sensitivity of less than or equal to 25 mIU/mL at the screening visit. This will be repeated at the Entry/Baseline visit.

Exclusion Criteria

• Pulmonary infection, acute COPD exacerbation, acute opportunistic infection within 30 days prior to the Screening Visit 1 or Entry/Baseline Visit 2.
• Any acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to the Entry/Baseline visit.
• Decompensated cirrhosis defined as an acute deterioration in liver function in a patient with cirrhosis and is characterized by jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome or variceal hemorrhage.
• History of, or planned, wedge resection, lobectomy, pneumonectomy, or lung volume reduction surgery.
• History of, or planned, endobronchial valve placement for lung volume reduction.
• Significant parenchymal lung disease other than emphysema or chronic bronchitis (e.g. sarcoidosis, MAI infection, pulmonary fibrosis, lung cancer, bullae/cysts from prior Pneumocystis pneumonia) that would preclude accurate quantification of emphysema.
• Previous allergy or intolerance to doxycycline or other drugs in the tetracycline class (e.g. minocycline, tetracycline).
• Breastfeeding individuals.
• Receipt of any investigational* drug within 30 days prior to the Entry/Baseline visit. Note: for the purpose of this protocol, investigational drug refers to a drug that is not FDA approved for any indication. COVID vaccines available under emergency use authorization are allowed.
• Need for concomitant use of barbiturates; carbamazepine; phenytoin
• Use of systemic retinoids (eg. Isotretinoin [Accutane]) or Vitamin A within 30 days prior to the Entry/Baseline visit. Note: Multivitamin containing Vitamin A use is permitted.
• Use of any systemic antibiotic (e.g., doxycycline or other tetracycline, azithromycin) within 7 days prior to the Entry/Baseline visit.
• 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.
• History of recurrent C. difficile infection or C. difficile infection within 30 days prior to the Entry/Baseline visit.
• Inability to stop supplemental oxygen for 15 minutes to perform a DLCO maneuver.
• Has changes to the chest that preclude adequate HRCT imaging (e.g. Metallic objects in the chest such as shrapnel or pacemaker leads)
• Current receipt of, or anticipated need to initiate, hemodialysis or peritoneal dialysis.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marshall J Glesby, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Cathie Spino, ScD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Robert J Kaner, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of California Los Angeles

Los Angeles, California, United States

University of California San Diego

San Diego, California, United States

Miami University

Miami, Florida, United States

Emory University

Atlanta, Georgia, United States

Tulane University

New Orleans, Louisiana, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

SUNY Downstate Medical School

Brooklyn, New York, United States

Weill Cornell Medicine

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Duke University School of Medicine

Durham, North Carolina, United States

University of Cincinnati College of Medicine

Cincinnati, Ohio, United States

Case Western University

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Temple University

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Texas, McGovern Medical School

Houston, Texas, United States

University of Washington

Seattle, Washington, United States

Countries

United States

Other Identifiers

DEPTH-001

Identifier Type: OTHER

Identifier Source: secondary_id

UH3HL154944

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22-02-307/22-04024723

Identifier Type: -

Identifier Source: org_study_id