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

NCT06477185 | Recruiting Phase 2 DMC

• 1 other identifier: Mak-SOMREC-2021-177
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

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.

Conditions

Tuberculosis, Pulmonary

Outcome Measures

Primary Outcomes (2)

• Mean High resolution CT (HRCT) fibrosis scores

  Quantified fibrosis scores (e.g. 0 - 25) will be derived from the CT interpretation tool, and recorded for each participant at baseline and 12 months' HRCT images, and compiled per treatment arm. Mean scores per study arm (intervention and control) will de determined for both baseline and 12 months' HRCT scans.

  12 months

• Efficacy of doxycycline as an anti-TB associated fibrosis agent

  This will be estimated or analyzed using analysis of covariance method. The difference in the mean 'total HRCT fibrosis score' between the intervention and control study arms shall be compared at 12 months adjusting for the total scores measured at baseline. A linear regression model shall be fit on log transformed values of total HRCT scores for each individual.

  12 months

Secondary Outcomes (3)

• Lung function assessment

  12 months

• Correlation between the High-Resolution CT fibrosis score and lung function assessment

  12 months

• comparison of trends of cytokines (matrix metalloproteinases and TGF beta) between intervention and control arm

  6 months

Study Arms (2)

Intervention: Doxycycline

EXPERIMENTAL

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

Drug: Doxycycline

Control arm

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Doxycycline 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.

Intervention: Doxycycline

Placebo DRUG

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

Control arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Makerere University: lead
• Makerere University Lung Institute: collaborator

Study Sites (2)

Makerere University Lung Institute

Kampala, Kampala, 00256, Uganda

NOT YET RECRUITING

Mulago National Referral Hospital

Kampala, 00256, Uganda

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Central Study Contacts

Ahmed Ddungu, MBCHB,MMED

CONTACT

0782303377; ahddungu@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized placebo-controlled trial

Study Record Dates

• First Submitted: August 10, 2023
• First Posted: June 27, 2024
• Study Start: December 4, 2024
• Primary Completion (Estimated): December 20, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After end of trial and publication of results
• Access Criteria: To any one who requests

Locations

UG (2)