Doxycycline in Human Pulmonary Tuberculosis
NCT02774993 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 40
Last updated 2017-11-27
Summary
Pulmonary cavitation, a hallmark of tuberculosis (TB), is the site of high mycobacterial burden leading to disease transmission. The cause of tissue destruction leading to cavitation in TB is primarily due to the host inflammatory response. A matrix degrading phenotype develops in TB, in which the activity of host proteolytic enzymes, specifically matrix metalloproteinases (MMPs) is unopposed by their specific Tissue Inhibitors of Metalloproteinases (TIMPs), thus driving tissue destruction and cavitation in TB. This tissue destruction causes morbidity and mortality. MMP inhibition with doxycycline has shown to improve lung function in patients with chronic lung diseases but its use in TB is unclear.
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
Conditions
Interventions
- DRUG
-
Doxycycline
- DRUG
Sponsors & Collaborators
-
Tan Tock Seng Hospital
collaborator OTHER -
National University of Singapore
collaborator OTHER -
A*Star
collaborator OTHER -
National University Hospital, Singapore
lead OTHER
Study Design
- Allocation
- RANDOMIZED
- Purpose
- TREATMENT
- Masking
- TRIPLE
- Model
- PARALLEL
Eligibility
- Min Age
- 21 Years
- Max Age
- 70 Years
- Sex
- ALL
- Healthy Volunteers
- Yes
Timeline & Regulatory
- Start
- 2015-09-30
- Primary Completion
- 2017-06-30
- Completion
- 2017-06-30
Countries
- Singapore
Study Locations
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