Tuberculosis, PulmonaryPhase 2TALF-TBNCT06477185
Characterization of Tuberculosis Associated Lung Fibrosis and Respiratory Impairment, and Prevention Using Doxycycline
A Phase 2 study testing Doxycycline in people with Tuberculosis, Pulmonary, run by Makerere University at 2 sites in Uganda.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tuberculosis, Pulmonary
- What is being tested?
- Doxycycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 2 sitesUganda
- Study dates
- 4 Dec 2024to Dec 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Uganda2 sites, 2 recruiting
- Not yet recruiting
Makerere University Lung Institute
Kampala, Kampala, 00256
Ahmed Ddungu, MBCHB,MMED, +256782303377, ahddungu@yahoo.com
Bruce Kirenga, MBCHB,PHD, 256782404431, brucekirenga@yahoo.co.uk
- Recruiting
Mulago National Referral Hospital
Kampala, 00256
Ahmed Ddungu, MBCHB, M.MED-Internal Medicine, +256782303377, ahddungu@yahoo.com
About this study
Official title: Characterization of Tuberculosis Associated Lung Fibrosis and Respiratory Impairment, and Prevention Using Doxycycline in A Double Blind Randomized Controlled Trial
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?
Read more
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.
Read the 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.
- Conditions
- Tuberculosis, Pulmonary
- Being tested
- Doxycycline, Placebo
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
Doxycycline is a bacteriostatic tetracycline antibiotic with ability to immunomodulate matrix metalloproteinases, enzymes well known to cause lung damage via breakdown lung extracellular matrix.
PlaceboDrug
This will be a chemically inert substance, designed to match oral doxycycline capsules but with no chemically active ingredients.
| Study group | Role | What they receive |
|---|---|---|
| Intervention: Doxycycline | Experimental | Oral doxycycline (100 mg) administered once daily for 12 weeks Receives: Drug: Doxycycline |
| Control arm | Placebo comparator | Oral placebo (matching with doxycycline) will be administered once daily for 12 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 months
Secondary outcomes (3)
Lung function assessment
Lung volumes including Forced expiratory volume in 1 second (FEV1), Forced vital capacity(FVC) will be obtained at spirometry for all subjects in both study arms (doxycycline and placebo) and compared with predicted values (standardized values for age, sex, race and smoking status) and results (percentage of predicted) compared across both study groups at 6 and 12 months.
Measured: 12 months
Correlation between the High-Resolution CT fibrosis score and lung function assessment
TB associated fibrosis will be quantified on CT using total scores derived a modified and adapted version of the Bhalla CT interpretation score for HRCTs done at baseline and 12 months. Lung function assessment will be by spirometry and will be derived as percentage predicted values of participants' lung volumes (FEV1, FVC) at 6 and 12 months and age, sex, race and smoking status standardized values. To estimate the correlation between the HRCT fibrosis score and the lung function assessment in each study arm (Doxycycline versus placebo); 3 log linear models shall be fit. These will include:
- Log linear model of interaction between FEV1 and treatment arm
- Log linear model of interaction between FVC and treatment arm
- Log linear model of interaction between FEV1/FVC ratio and treatment arm
Measured: 12 months
comparison of trends of cytokines (matrix metalloproteinases and TGF beta) between intervention and control arm
Serum concentrations of matrix metalloproteinases (MMPs 1, 3, 8, 9) and Transforming growth factor beta 1 (TGFβ1) will be measured in ng/ml at baseline, 3 and 6 months. Means of the MMP concentrations will be calculated and compared between intervention and placebo arm (at baseline, 3 and 6 months) and analyzed using repeated analysis of variance and mixed effect model.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2024
- Study start4 Dec 2024
- Primary completion20 Dec 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis, PulmonaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Makerere University
- Sponsor type
- University, hospital or other
- Collaborators
- Makerere University Lung Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06477185
- Sponsor's protocol ID
- Mak-SOMREC-2021-177
- Acronym
- TALF-TB
- Status last verified
- Apr 2025
- First submitted
- 10 Aug 2023
- Last updated
- 17 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participants' data collected during the trial will be available for sharing after deidentification.