Ignite Creation Date:
2025-12-25 @ 1:04 AM
Ignite Modification Date:
2026-01-05 @ 5:35 PM
Study NCT ID:
NCT02774993
Status:
COMPLETED
Last Update Posted:
2017-11-27
First Post:
2016-03-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Doxycycline in Human Pulmonary Tuberculosis
Sponsor:
National University Hospital, Singapore
Organization:
Study Overview
Official Title:
Doxycycline and the Modulation of Host Immunopathology in Human Pulmonary Tuberculosis: A Pilot Study
Status:
COMPLETED
Status Verified Date:
2016-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Doxy-TB
Brief 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
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:
All TB patients are to keep to their standard anti-tuberculous treatment. A standardized questionnaire of symptoms, side-effects and weight shall be recorded. Induced sputum and plasma samples from all TB patients shall be analysed for MMPs and TIMPs before and after the administration of doxycycline for two weeks. In addition, neutrophils and mononuclear cells from TB patients and these shall be stimulated with live, virulent M. tuberculosis in a Biosafety Level 3 laboratory. The supernatants from these cells shall be analysed for MMPs and TIMPs.
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: