Summary

Eligibility
for people ages 30 years and up (full criteria)
Location
at San Diego, California and other locations
Dates
study started
estimated completion

Description

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.

Details

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.

Keywords

Emphysema, HIV, Pulmonary Emphysema, Doxycycline

Eligibility

You can join if…

Open to people ages 30 years and up

  • 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. Emphysema is defined as 5 to 35% of voxels with density < -950 Hounsfield Units (HU).
  • Low DLCO, defined as average of screening and pre-entry measurements < LLN (lower bound of the 95% confidence interval for the normal predicted value) of the Global Lung Initiative (GLI) predicted set for DLCO adjusted for barometric pressure. Screening and pre-entry measurements must be within 10% of each other.
  • 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 > 200 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.
  • Calculated creatinine clearance (CrCl) greater than or equal to 60 mL/min as estimated by the Cockcroft-Gault equation within 45 days prior to the Entry/Baseline visit.
  • Serum ALT and AST < 3 x upper limit of normal within 45 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.

You CAN'T join if...

  • Pulmonary infection, acute COPD exacerbation, acute opportunistic infection within 30 days prior to the Entry/Baseline visit.
  • 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).
  • 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.
  • History of Pneumocystis pneumonia.
  • 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)

Locations

  • University of California San Diego accepting new patients
    San Diego California 92103 United States
  • University of California Los Angeles not yet accepting patients
    Los Angeles California 90095 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Weill Medical College of Cornell University
ID
NCT05382208
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 250 study participants
Last Updated