Characterization of Tuberculosis Associated Lung Fibrosis and Respiratory Impairment, and Prevention Using Doxycycline (TALF-TB)

Makerere University

Status and phase: Enrolling; Phase 2

Conditions: Tuberculosis, Pulmonary

Treatments: Drug: Placebo; Drug: Doxycycline

Study type: Interventional

Funder types: Other

Identifiers

NCT06477185

Mak-SOMREC-2021-177

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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200 participants in 2 patient groups, including a placebo group

Intervention: Doxycycline

Experimental group

Description:

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

Treatment:

Drug: Doxycycline

Control arm

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo