Clinical trial NCT06477185: Characterization of Tuberculosis Associated Lung Fibrosis and Respiratory Impairment, and Prevention Using Doxycycline
Official title: Characterization of Tuberculosis Associated Lung Fibrosis and Respiratory Impairment, and Prevention Using Doxycycline in A Double Blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Tuberculosis, Pulmonary
Lead sponsor: Makerere University
Sponsor class: OTHER
Collaborators: name: Makerere University Lung Institute
First posted: 2024-06-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized placebo-controlled trial
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* 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 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 the trial drug.
* Known allergies to doxycycline or other tetracyclines
* Known autoimmune disease
* Any factor felt to significantly increase risk of adverse event

Primary outcomes:
measure: Mean High resolution CT (HRCT) fibrosis scores
timeFrame: 12 months
measure: Efficacy of doxycycline as an anti-TB associated fibrosis agent
timeFrame: 12 months
Secondary outcomes:
measure: Lung function assessment
timeFrame: 12 months
measure: Correlation between the High-Resolution CT fibrosis score and lung function assessment
timeFrame: 12 months
measure: comparison of trends of cytokines (matrix metalloproteinases and TGF beta) between intervention and control arm
timeFrame: 6 months
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Makerere University Lung Institute
city: Kampala
country: Uganda
facility: Mulago National Referral Hospital
Study officials:
References: