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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 65 Years
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06477185
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Makerere University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Uganda
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Tuberculosis, Pulmonary

Additional Details

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.

Arms & Interventions

Arms

Experimental: Intervention: Doxycycline

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

Placebo Comparator: Control arm

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

Interventions

Drug: - 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.

Drug: - Placebo

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.