NCT05382208

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
133

participants targeted

Target at P75+ for phase_2

Timeline
9mo left

Started Aug 2022

Typical duration for phase_2

Geographic Reach
1 country

20 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress83%
Aug 2022Feb 2027

First Submitted

Initial submission to the registry

May 16, 2022

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 19, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

August 22, 2022

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2027

Last Updated

January 26, 2026

Status Verified

January 1, 2026

Enrollment Period

4.4 years

First QC Date

May 16, 2022

Last Update Submit

January 22, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Rate of decline (slope) of percent predicted diffusing capacity for carbon monoxide (DLCO) corrected for hemoglobin, carboxyhemoglobin and barometric pressure (indicated as ppDLCOadj) over the 72 week treatment period.

    72 weeks

Secondary Outcomes (22)

  • Change from baseline to week 48 in 6 minute walk test distance.

    48 weeks

  • Change from baseline to week 72 in 6 minute walk test distance.

    72 weeks

  • Change from baseline to week 48 in percent predicted diffusing capacity for carbon monoxide (DLCO) corrected for hemoglobin, carboxyhemoglobin and barometric pressure (ppDLCOadj).

    48 weeks

  • Change from baseline to week 72 in percent predicted diffusing capacity for carbon monoxide (DLCO) corrected for hemoglobin, carboxyhemoglobin and barometric pressure (ppDLCOadj).

    72 weeks

  • Change from baseline to week 72 in percentage of voxels < -950 Hounsfield Units (HU)

    72 weeks

  • +17 more secondary outcomes

Study Arms (2)

Doxycycline

EXPERIMENTAL

Doxycycline 100mg orally twice a day

Drug: Doxycycline

Placebo

PLACEBO COMPARATOR

Matching placebo orally twice a day

Drug: Placebo

Interventions

Doxycycline 100 mg orally twice a day.

Doxycycline

Matching placebo orally twice a day.

Placebo

Eligibility Criteria

Age30 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • Mild, moderate, or severe emphysema assessed by central reader(s) at the CT Imaging Core; or
  • 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.
  • Screening (Visit 1) Pulmonary Function Test meets ATS quality criteria as determined by a central reviewer at the PFT Reading Core (UCLA)
  • 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.
  • +6 more criteria

You may not qualify if:

  • 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.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

Miami University

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

SUNY Downstate Medical School

Brooklyn, New York, 11203, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27704, United States

Location

University of Cincinnati College of Medicine

Cincinnati, Ohio, 45267, United States

Location

Case Western University

Cleveland, Ohio, 44106, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

University of Texas, McGovern Medical School

Houston, Texas, 77030, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Emphysema

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

TetracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Study Officials

  • Marshall J Glesby, MD, PhD

    Weill Medical College of Cornell University

    PRINCIPAL INVESTIGATOR
  • Cathie Spino, ScD

    University of Michigan

    PRINCIPAL INVESTIGATOR
  • Robert J Kaner, MD

    Weill Medical College of Cornell University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
The participant and site personnel will not know which study treatment the participant is receiving.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 16, 2022

First Posted

May 19, 2022

Study Start

August 22, 2022

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

February 1, 2027

Last Updated

January 26, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

The de-identified analytic data will be prepared as SAS transport files or ASCII comma-delimited files with accompanying codebooks that describe the data and data structure. The redaction will employ best practices and will be consistent with NHLBI data sharing policies.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Study data will be shared through the NHLBI data repository, no later than 3 years after the end of the study or 2 years after the main paper reporting the results of the trial, whichever comes first.
Access Criteria
Data will be shared through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC).
More information

Locations