ACTIVE_NOT_RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2022-08-22

Study Completion:2027-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05382208

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * 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.	* 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.

Inclusion Criteria

Exclusion 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.
* 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.

* 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.

Contacts and Locations

Principal Investigator

Marshall J Glesby, MD, PhD

PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Cathie Spino, ScD

PRINCIPAL_INVESTIGATOR

University of Michigan

Robert J Kaner, MD

PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35233

United States

University of California Los Angeles

Los Angeles, California, 90095

United States

University of California San Diego

San Diego, California, 92103

United States

Miami University

Miami, Florida, 33136

United States

Emory University

Atlanta, Georgia, 30329

United States

Tulane University

New Orleans, Louisiana, 70112

United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Washington University School of Medicine

St Louis, Missouri, 63110

United States

SUNY Downstate Medical School

Brooklyn, New York, 11203

United States

Weill Cornell Medicine

New York, New York, 10065

United States

University of North Carolina

Chapel Hill, North Carolina, 27514

United States

Duke University School of Medicine

Durham, North Carolina, 27704

United States

University of Cincinnati College of Medicine

Cincinnati, Ohio, 45267

United States

Case Western University

Cleveland, Ohio, 44106

United States

Ohio State University

Columbus, Ohio, 43210

United States

Temple University

Philadelphia, Pennsylvania, 19140

United States

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261

United States

University of Texas, McGovern Medical School

Houston, Texas, 77030

United States

University of Washington

Seattle, Washington, 98104

United States

Collaborators and Investigators

Sponsor: Weill Medical College of Cornell University

Marshall J Glesby, MD, PhD, PRINCIPAL_INVESTIGATOR, Weill Medical College of Cornell University
Cathie Spino, ScD, PRINCIPAL_INVESTIGATOR, University of Michigan
Robert J Kaner, MD, PRINCIPAL_INVESTIGATOR, Weill Medical College of Cornell University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-08-22

Study Completion Date2027-02

Study Record Updates

Study Start Date2022-08-22

Study Completion Date2027-02

Terms related to this study

Additional Relevant MeSH Terms

Emphysema
HIV