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

Last updated: April 14, 2025
Sponsor: Makerere University
Overall Status: Active - Recruiting

Phase

2

Condition

Cystic Fibrosis

Lung Injury

Hiv

Treatment

Placebo

Doxycycline

Clinical Study ID

NCT06477185
Mak-SOMREC-2021-177
  • Ages 18-65
  • All Genders

Study 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 Criteria

Inclusion

Inclusion Criteria:

  • Age of 18 - 65 years

  • Index PTB episode (sputum smear positive or GeneXpert positive with rifampicinsusceptibility)

  • 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

Exclusion Criteria:

  • 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 thetrial drug.

  • Known allergies to doxycycline or other tetracyclines

  • Known autoimmune disease

  • Any factor felt to significantly increase risk of adverse event

Study Design

Total Participants: 200
Treatment Group(s): 2
Primary Treatment: Placebo
Phase: 2
Study Start date:
December 04, 2024
Estimated Completion Date:
December 31, 2027

Study Description

This will be a double-blind randomized block stratified clinical trial. Participants will be enrolled if they have advanced drug sensitive TB evidenced by infiltrates/lesions in at least 2 zones on a chest X-ray, among other inclusion criteria.

Participants will receive 100mg of doxycycline or matching placebo once a day for 12 weeks in addition to standard anti TB therapy.

Participants will undergo baseline high resolution CT scans to evaluate lung parenchyma involvement and repeat CT scans at 12 months to score TB associated fibrosis.

Lung function assessment with spirometry will be done at 6 and 12 months after enrolment to assess trends of lung function in the control and intervention study arms.

Profibrotic cytokines (TGFbeta) and Matrix metalloproteinases (1, 3 ,8,9) will be measured at baseline , 3 and 6 months after enrolment.

Connect with a study center

  • Makerere University Lung Institute

    Kampala, 00256
    Uganda

    Site Not Available

  • Mulago National Referral Hospital

    Kampala, 00256
    Uganda

    Active - Recruiting

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