A Phase 2 interventional study of Doxycycline and Placebo in Tuberculosis, Pulmonary, sponsored by Makerere University. Recruiting at 2 sites in Uganda. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-04-17.
Sponsored by Makerere University · Phase 2, Interventional, and Treatment
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:
Participants will be subjected to the following:
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.
319 studies on the registry are indexed under Tuberculosis, Pulmonary; 71 are open to participants now.
This study's planned enrollment of 200 is above the median of 146 across 227 interventional studies indexed under Tuberculosis, Pulmonary.
Browse Tuberculosis, Pulmonary studies →Makerere University is the lead sponsor of 144 studies on the registry; 16 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Oral doxycycline (100 mg) administered once daily for 12 weeks
Drug: Doxycycline
Oral placebo (matching with doxycycline) will be administered once daily for 12 weeks
Drug: Placebo
Doxycycline is a bacteriostatic tetracycline antibiotic with ability to immunomodulate matrix metalloproteinases, enzymes well known to cause lung damage via breakdown lung extracellular matrix.
This will be a chemically inert substance, designed to match oral doxycycline capsules but with no chemically active ingredients.
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.
Time frame: 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.
Time frame: 12 months
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.
Time frame: 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
Time frame: 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.
Time frame: 6 months
Plan to share: Yes — All individual participants' data collected during the trial will be available for sharing after deidentification.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: After end of trial and publication of results
Access criteria: To any one who requests
No publications or documents are linked to this record.
Started Dec 2024 (actual). Primary completion is estimated for Dec 2026, 24 months after the start.
Of 33 non-industry phase 2 interventional studies under Tuberculosis, Pulmonary, half reached primary completion within 30 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 49. This study's planned 24 months is below that.
Counting every sponsor, half of 43 studies reached it within 30 months; a quarter within 21 and three quarters within 37.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Doxycycline