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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-04

Study Completion Date

2027-12-31

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Tuberculosis, Pulmonary

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized placebo-controlled trial

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Double blind study

Study Groups

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Intervention: Doxycycline

Oral doxycycline (100 mg) administered once daily for 12 weeks

Group Type EXPERIMENTAL

Doxycycline

Intervention Type DRUG

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

Control arm

Oral placebo (matching with doxycycline) will be administered once daily for 12 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Doxycycline

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No