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

HIV Clinical Trial

— DEPTH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05382208
• Other study ID #: 22-02-307/22-04024730
• Secondary ID: DEPTH-001UG3HL15
• Status: Recruiting
• Phase: Phase 2
• Start date: August 22, 2022
• Est. completion date: February 2027

Study information

• Verified date: June 2024
• Source: Weill Medical College of Cornell University
• Contact: Robert J Kaner, MD
• Phone: 646-962-2333
• Email: rkaner[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: February 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Emphysema
• HIV
• Pulmonary Emphysema

Intervention

Drug:
• Doxycycline
Doxycycline 100 mg orally twice a day.
• Placebo
Matching placebo orally twice a day.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	SUNY Downstate Medical School	Brooklyn	New York
United States	The University of North Carolina	Chapel Hill	North Carolina
United States	University of Cincinnati College of Medicine	Cincinnati	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Duke University School of Medicine	Durham	North Carolina
United States	University of Texas, McGovern Medical School	Houston	Texas
United States	University of California Los Angeles	Los Angeles	California
United States	Miami University	Miami	Florida
United States	Tulane University	New Orleans	Louisiana
United States	Weill Cornell Medicine	New York	New York
United States	Temple University	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of California San Diego	San Diego	California
United States	University of Washington	Seattle	Washington
United States	DC VAMC	Washington	District of Columbia

Sponsors (5)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	National Heart, Lung, and Blood Institute (NHLBI), University of California, Los Angeles, University of Iowa, University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from baseline to week 48 in 6 minute walk test distance.		48 weeks
Secondary	Change from baseline to week 72 in 6 minute walk test distance.		72 weeks
Secondary	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
Secondary	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
Secondary	Change from baseline to week 72 in percentage of voxels < -950 Hounsfield Units (HU)		72 weeks
Secondary	Change from baseline to week 48 in the COPD Activity Test (CAT) score	The COPD Assessment Test (CAT): CAT is an 8-item self-administered questionnaire. Scores range from 0 to 40. Higher scores denote a more severe impact of COPD on a patient's life.	48 weeks
Secondary	Change from baseline to week 72 in the COPD Activity Test (CAT) score	The COPD Assessment Test (CAT): CAT is an 8-item self-administered questionnaire. Scores range from 0 to 40. Higher scores denote a more severe impact of COPD on a patient's life.	72 weeks
Secondary	Change from baseline to week 48 in St. George's Respiratory Questionnaire (SGRQ) score	St. George's Respiratory Questionnaire (SGRQ): SGRQ is a 50-item respiratory disease-specific health-related quality of life (HRQOL) instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.	48 weeks
Secondary	Change from baseline to week 72 in St. George's Respiratory Questionnaire (SGRQ) score	St. George's Respiratory Questionnaire (SGRQ): SGRQ is a 50-item respiratory disease-specific health-related quality of life (HRQOL) instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.	72 weeks
Secondary	Change from baseline to week 48 in forced expiratory volume in 1 second (FEV1) (L)		48 weeks
Secondary	Change from baseline to week 72 in forced expiratory volume in 1 second (FEV1) (L)		72 weeks
Secondary	Change from baseline to week 48 in the ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC)		48 weeks
Secondary	Change from baseline to week 72 in the ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC)		72 weeks
Secondary	The number of adverse events	The number of adverse events regardless of relatedness to the intervention	72 weeks
Secondary	The proportion of participants with at least 1 adverse event	The proportion of participants with at least 1 adverse event regardless of relatedness to the intervention	72 weeks
Secondary	The number of serious adverse events.	Serious adverse events (SAEs) will include all treatment-emergent SAEs.	72 weeks
Secondary	The proportion of participants with at least 1 serious adverse event.	The proportion of participants with at least 1 Serious adverse event (SAE). SAEs will include all treatment-emergent SAEs.	72 weeks
Secondary	The proportion of participants with deaths.		72 weeks
Secondary	The number of participants permanently discontinuing study medication due to adverse events.	The number of participants permanently discontinuing study medication due to treatment-emergent adverse events.	72 weeks
Secondary	The proportion of participants permanently discontinuing study medication due to adverse events.	The proportion of participants permanently discontinuing study medication due to treatment-emergent adverse events.	72 weeks
Secondary	The number of participants with development of culture proven antibiotic-resistant bacterial infection with reduced susceptibility or resistance to doxycycline (adverse event of special interest).		72 weeks
Secondary	The proportion of participants with development of culture proven antibiotic-resistant bacterial infection with reduced susceptibility or resistance to doxycycline (adverse event of special interest).		72 weeks