Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
40 participants
INTERVENTIONAL
2015-09-30
2017-06-30
Brief Summary
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We hypothesise that the MMP inhibitor doxycycline will reduce tissue destruction in human pulmonary tuberculosis.
Specific aims:
* To investigate the MMP and TIMP secretion and gene expression in M. tuberculosis (M.tb) - infected primary neutrophils and monocytes from healthy volunteers taking doxycycline.
* To investigate the intracellular signaling pathways modulated by doxycycline
* To investigate the effects doxycycline has on biological markers of tissue destruction in TB patients
* To assess the tolerability and side effects of doxycycline with concurrent standard TB therapy
Detailed Description
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Healthy volunteers shall be recruited and administered doxycycline for 2 weeks. Neutrophils and mononuclear cells will be isolated from blood prior to treatment, at weeks 2 and 8 and infected with M.tb. Cell culture supernatants and nucleic acids will be harvested. MMP and TIMP expression will be analysed using luminex array and real-time polymerase chain reaction. Intracellular signaling pathways will be examined with a human phospho-kinase array. Matrix destruction will be assessed using collagen quantitative fluorescent assays.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Doxycycline
Doxycycline 100 mg twice daily with once daily anti-tuberculous treatment comprising of rifampicin 10 mg/kg, isoniazid 5 mg/kg, ethambutol 20 mg/kg, pyrazinamide 25 mg/kg and pyridoxine 10-50 mg per day according to managing physicians' discretion. These will be given daily for 14 days. Subsequently doxycycline will be ceased and patients are to continue with their standard anti-tuberculous treatment and duration according to their managing physician
Doxycycline
Placebo
Placebo twice daily with once daily anti-tuberculous treatment comprising of rifampicin 10 mg/kg, isoniazid 5 mg/kg, ethambutol 20 mg/kg, pyrazinamide 25 mg/kg and pyridoxine 10-50 mg per day according to managing physicians' discretion. These will be given daily for 14 days. Subsequently placebo will be ceased and patients are to continue with their standard anti-tuberculous treatment and duration according to their managing physician
placebo
Interventions
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Doxycycline
placebo
Eligibility Criteria
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Inclusion Criteria
2. Aged 21 years to less than 70.
1. Patients receiving ≤ 7 days of TB treatment or about to start standard combination TB treatment
2. Confirmed pulmonary TB with positive acid-fast bacilli smear and/or positive TB GeneXpert test and/or culture results
3. Chest radiograph demonstrating pulmonary involvement
4. Aged 21 years to less than 70
Exclusion Criteria
2. Prisoners
3. Pregnancy or nursing
4. On medication or oral contraceptives
5. Any concurrent illness, such as influenza
TB patients
1. HIV co-infection
2. Previous pulmonary TB
3. Severe, pre-existing lung disease such as pulmonary fibrosis, bronchiectasis, Chronic obstructive pulmonary disease and lung cancer
4. Pregnant or breast feeding
5. Allergies to tetracyclines
6. Patients on retinoic acid, neuromuscular blocking agents and pimozide which may increase risk of drug toxicity
7. Autoimmune disease and/or on systemic immunosuppressants
8. Unable to provide informed consent
9. Haemoglobin \< 8 g/dl
10. Creatinine 2 times upper limit of normal (ULN)
11. Alanine transaminase \>3 times ULN
12. Use of any investigational or non-registered drug, vaccine or medical device other than the study drug within 182 days preceding dosing of study drug, or planned use during the study period
13. Enrolment in any other clinical trial involving a systemic drug or intervention involving the lung
14. Evidence of severe depression, schizophrenia or mania
15. Principal investigator assessment of lack of willingness to participate and comply with all requirements of the protocol, or identification of any factor felt to significantly increase the participant's risk of suffering an adverse outcome
21 Years
70 Years
ALL
Yes
Sponsors
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Tan Tock Seng Hospital
OTHER
National University of Singapore
OTHER
A*Star
OTHER
National University Hospital, Singapore
OTHER
Responsible Party
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Locations
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National University Hospital
Singapore, , Singapore
Countries
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References
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Miow QH, Vallejo AF, Wang Y, Hong JM, Bai C, Teo FS, Wang AD, Loh HR, Tan TZ, Ding Y, She HW, Gan SH, Paton NI, Lum J, Tay A, Chee CB, Tambyah PA, Polak ME, Wang YT, Singhal A, Elkington PT, Friedland JS, Ong CW. Doxycycline host-directed therapy in human pulmonary tuberculosis. J Clin Invest. 2021 Aug 2;131(15):e141895. doi: 10.1172/JCI141895.
Other Identifiers
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Doxy_TB
Identifier Type: -
Identifier Source: org_study_id