RecruitingPhase 2NCT06477185

Characterization of Tuberculosis Associated Lung Fibrosis and Respiratory Impairment, and Prevention Using Doxycycline

Characterization of Tuberculosis Associated Lung Fibrosis and Respiratory Impairment, and Prevention Using Doxycycline in A Double Blind Randomized Controlled Trial


Sponsor

Makerere University

Enrollment

200 participants

Start Date

Dec 4, 2024

Study Type

INTERVENTIONAL

Conditions

Summary

The goal of this clinical trial is to assess the efficacy(effectiveness) of doxycycline, a potent inhibitor of matrix metalloproteinase (lung collagenase) activity in prevention of Tuberculosis associated lung fibrosis and associated lung function decline among patients with drug sensitive advanced TB. The main question\[s\] it aims to answer are: * Does doxycycline have a significant anti-fibrosis role when given as adjuvant therapy to TB patients with advanced pulmonary TB in a double blind randomized placebo controlled trial? * How does long term respiratory function defer between patients who received adjuvant doxycycline aimed at prevention of TB associated lung fibrosis and those who received a placebo in a double blind randomized controlled trial? Participants will be subjected to the following: * Experimental arm: Doxycycline 100 mg once daily for 12 weeks administered concurrently with standard of care anti-TBs. * Comparator arm: Placebo once daily for 12 weeks administered concurrently with standard of care anti-TBs.


Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria6

  • Age of 18 - 65 years
  • Index PTB episode (sputum smear positive or GeneXpert positive with rifampicin susceptibility)
  • Baseline CXR showing infiltrates in at least 2 lung zones (≥30% lung involvement) meeting criteria for moderate/advanced PTB
  • HIV uninfected
  • Subjects willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Able to give written informed consent.

Exclusion Criteria11

  • Pregnancy
  • Breastfeeding
  • Baseline serum creatinine or liver enzymes >2 times above upper limit of normal
  • Taking corticosteroids for ≥14 days or anti-TBs >7days
  • Prospects already enrolled in another clinical trial
  • Diabetic patients (most diabetics are on metformin or have history of metformin use. Metformin is postulated to have an anti-fibrosis role)
  • Patients with malignancy or on anticancer medication
  • Situation where a participant is taking a drug/medication known to interact with the trial drug.
  • Known allergies to doxycycline or other tetracyclines
  • Known autoimmune disease
  • Any factor felt to significantly increase risk of adverse event

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Interventions

DRUGDoxycycline

Doxycycline is a bacteriostatic tetracycline antibiotic with ability to immunomodulate matrix metalloproteinases, enzymes well known to cause lung damage via breakdown lung extracellular matrix.

DRUGPlacebo

This will be a chemically inert substance, designed to match oral doxycycline capsules but with no chemically active ingredients.


Locations(2)

Makerere University Lung Institute

Kampala, Kampala, Uganda

Mulago National Referral Hospital

Kampala, Uganda

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NCT06477185


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