Latency in Pulmonary Tuberculosis

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ClinicalTrials.gov Identifier: NCT01154959

Recruitment Status : Unknown

Verified June 2011 by Tuberculosis Research Centre, India.
Recruitment status was: Recruiting

First Posted : July 1, 2010

Last Update Posted : June 16, 2011

Sponsor:

Collaborator:

National Institutes of Health (NIH)

Information provided by:

Tuberculosis Research Centre, India

Study Description

Brief Summary:

The immune responses in latent tuberculosis are poorly understood. While it is difficult to define the onset of latency during natural infection, patients undergoing treatment for tuberculosis are driven into a state of latency or cure. The present study on the effect of 3 and 4 month regimens containing moxifloxacin in sputum smear and culture positive pulmonary tuberculosis (TRC Study number 24) offers us the opportunity to study definitive immune responses pre and post treatment. We will evaluate a variety of innate and adaptive immune responses in patients before and after treatment and our study will compare the differences in immuno-phenotype (eg. Markers of T, B and NK cell activation, proliferation and regulatory phenotype) and function (eg. Production of cytokines, proliferative responses to TB antigens) at different time points following treatment. In addition, since a small percentage of patients will undergo relapse following treatment, the kinetics of immune responses in these patients will used to assess immunological predictors of relapse in tuberculosis.

Condition or disease	Intervention/treatment	Phase
Pulmonary Tuberculosis	Drug: Moxifloxacin, Isoniazid, Rifampicin Pyrazinamide, Ethambutol	Phase 3

Show Detailed Description

Study Design


Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	200 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Characterization of Immune Responses in Treatment-induced Latency in Pulmonary Tuberculosis
Study Start Date :	February 2010
Estimated Primary Completion Date :	February 2013
Estimated Study Completion Date :	February 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Drug Information available for: Isoniazid Ethambutol Pyrazinamide Moxifloxacin

Genetic and Rare Diseases Information Center resources: Tuberculosis

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Regimen 1 Rifampicin, isoniazid, pyrazinamide, ethambutol and moxifloxacin daily for 3 months (3RHZEM)	Drug: Moxifloxacin, Isoniazid, Rifampicin Pyrazinamide, Ethambutol Moxifloxacin (400mg), Isoniazid (300mg daily, 600mg thrice weekly), Rifampicin (450mg, and 600mg for patients weighing 60kg or more), Pyrazinamide (1500mg), Ethambutol (800mg)
Experimental: Regimen 2 Rifampicin, isoniazid, pyrazinamide, ethambutol and moxifloxacin daily for 2 months followed by rifampicin, isoniazid, and moxifloxacin daily for 2 months (2 RHZEM daily / 2 RHM daily)	Drug: Moxifloxacin, Isoniazid, Rifampicin Pyrazinamide, Ethambutol Moxifloxacin (400mg), Isoniazid (300mg daily, 600mg thrice weekly), Rifampicin (450mg, and 600mg for patients weighing 60kg or more), Pyrazinamide (1500mg), Ethambutol (800mg)
Experimental: Regimen 3 Rifampicin, isoniazid, pyrazinamide, ethambutol and moxifloxacin daily for 2 months followed by rifampicin, isoniazid, and moxifloxacin thrice weekly for 2 months (2 RHZEM daily / 2RHM thrice weekly)	Drug: Moxifloxacin, Isoniazid, Rifampicin Pyrazinamide, Ethambutol Moxifloxacin (400mg), Isoniazid (300mg daily, 600mg thrice weekly), Rifampicin (450mg, and 600mg for patients weighing 60kg or more), Pyrazinamide (1500mg), Ethambutol (800mg)
Experimental: Regimen 4 Rifampicin, isoniazid, pyrazinamide, ethambutol and moxifloxacin daily for 2 months followed by rifampicin, isoniazid, ethambutol and moxifloxacin thrice weekly for 2 months (2 RHZEM daily / 2 RHEM thrice weekly)	Drug: Moxifloxacin, Isoniazid, Rifampicin Pyrazinamide, Ethambutol Moxifloxacin (400mg), Isoniazid (300mg daily, 600mg thrice weekly), Rifampicin (450mg, and 600mg for patients weighing 60kg or more), Pyrazinamide (1500mg), Ethambutol (800mg)
Active Comparator: Control Regimen Rifampicin, isoniazid, pyrazinamide and ethambutol thrice weekly for 2 months followed by rifampicin and isoniazid thrice weekly for 4 months (2 RHZE thrice weekly / 4 RH thrice weekly)	Drug: Moxifloxacin, Isoniazid, Rifampicin Pyrazinamide, Ethambutol Moxifloxacin (400mg), Isoniazid (300mg daily, 600mg thrice weekly), Rifampicin (450mg, and 600mg for patients weighing 60kg or more), Pyrazinamide (1500mg), Ethambutol (800mg)

Outcome Measures

Primary Outcome Measures :

The immune response to crude antigens - PPD and CFA and defined antigens - ESAT-6 and CFP-10 as well as positive controls- SEB and anti-CD3. [ Time Frame: 2 years ]

Secondary Outcome Measures :

Determining the correlation of increase in regulatory factors with the development of relapse in treated TB patients. [ Time Frame: 2 years ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18 years and above
Residing in or around Chennai or Madurai
No anti-TB treatment in the past or should have had less than one month of treatment (but less than one week in the preceding one month before enrollment in the study)
At least two sputum smears should be positive for tubercle bacilli by fluorescent microscopy
Express willingness to attend the treatment centre for supervised treatment
Express willingness for home visits by the staff of the centre
Express willingness to give written informed consent

Exclusion Criteria:

Body weight less than 30 kg
Hepatic or renal disease as evidenced by clinical or biochemical abnormalities
Diabetes mellitus
A history of seizure or loss of consciousness
Psychiatric illness
An abnormal electrocardiogram or anti-arrhythmic medication
Those in a moribund state
Sero-positive for HIV antibodies
Pregnancy or lactation
Visual disorders other than refractory error

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01154959

Contacts


Contact: Subash Babu, MBBS, PhD	91-44-28369711	sbabu@niaid.nih.gov
Contact: Pavan Kumar, MSc	91-44-28369766	pavankumarn@trcchennai.in

Locations


India
Tuberculosis Research Centre	Recruiting
Chennai, Tamilnadu, India, 600031
Contact: Subash Babu, MBBS, PhD 91-44-28369711 sbabu@niaid.nih.gov
Contact: Pavan Kumar, MSc 91-44-28369766 pavankumarn@trcchennai.in
Principal Investigator: Subash Babu, MBBS, PhD

Sponsors and Collaborators

Tuberculosis Research Centre, India

National Institutes of Health (NIH)

Investigators


Principal Investigator:	Subash Babu, MBBS, PhD	Tuberculosis Research Centre, India

More Information

Publications:

Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol. 1974 Feb;99(2):131-8.

Lillebaek T, Dirksen A, Baess I, Strunge B, Thomsen VØ, Andersen AB. Molecular evidence of endogenous reactivation of Mycobacterium tuberculosis after 33 years of latent infection. J Infect Dis. 2002 Feb 1;185(3):401-4. Epub 2002 Jan 17.

Wayne LG, Sohaskey CD. Nonreplicating persistence of mycobacterium tuberculosis. Annu Rev Microbiol. 2001;55:139-63. Review.

EDWARDS PQ, EDWADS LB. Story of the tuberculin test from an epidemiologic viewpoint. Am Rev Respir Dis. 1960 Jan;81(1)Pt 2:1-47.

Kaufmann SH. How can immunology contribute to the control of tuberculosis? Nat Rev Immunol. 2001 Oct;1(1):20-30. Review.

Lin MY, Ottenhoff TH. Not to wake a sleeping giant: new insights into host-pathogen interactions identify new targets for vaccination against latent Mycobacterium tuberculosis infection. Biol Chem. 2008 May;389(5):497-511. Review.

Ulrichs T, Kaufmann SH. New insights into the function of granulomas in human tuberculosis. J Pathol. 2006 Jan;208(2):261-9. Review.

Khader SA, Cooper AM. IL-23 and IL-17 in tuberculosis. Cytokine. 2008 Feb;41(2):79-83. doi: 10.1016/j.cyto.2007.11.022. Epub 2008 Jan 22. Review.

North RJ, Jung YJ. Immunity to tuberculosis. Annu Rev Immunol. 2004;22:599-623. Review.

Locht C, Rouanet C, Hougardy JM, Mascart F. How a different look at latency can help to develop novel diagnostics and vaccines against tuberculosis. Expert Opin Biol Ther. 2007 Nov;7(11):1665-77. Review.

Murphy KM, Reiner SL. The lineage decisions of helper T cells. Nat Rev Immunol. 2002 Dec;2(12):933-44. Review.

Dong C. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008 May;8(5):337-48. doi: 10.1038/nri2295. Review.

McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity. 2008 Apr;28(4):445-53. doi: 10.1016/j.immuni.2008.03.001. Review.

Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol. 2007;25:821-52. Review.

Fontenot JD, Rudensky AY. Molecular aspects of regulatory T cell development. Semin Immunol. 2004 Apr;16(2):73-80. Review.

Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004;22:531-62. Review.

Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515-48. Review.

Li MO, Flavell RA. Contextual regulation of inflammation: a duet by transforming growth factor-beta and interleukin-10. Immunity. 2008 Apr;28(4):468-76. doi: 10.1016/j.immuni.2008.03.003. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kumar NP, Moideen K, Dhakshinraj SD, Banurekha VV, Nair D, Dolla C, Kumaran P, Babu S. Profiling leucocyte subsets in tuberculosis-diabetes co-morbidity. Immunology. 2015 Oct;146(2):243-50. doi: 10.1111/imm.12496. Epub 2015 Jul 6.

Kumar NP, Sridhar R, Nair D, Banurekha VV, Nutman TB, Babu S. Type 2 diabetes mellitus is associated with altered CD8(+) T and natural killer cell function in pulmonary tuberculosis. Immunology. 2015 Apr;144(4):677-86. doi: 10.1111/imm.12421.


Responsible Party:	Dr. S. Subash Babu, Tuberculosis Research Centre (ICMR)
ClinicalTrials.gov Identifier:	NCT01154959 History of Changes
Other Study ID Numbers:	LTB01
First Posted:	July 1, 2010 Key Record Dates
Last Update Posted:	June 16, 2011
Last Verified:	June 2011

Keywords provided by Tuberculosis Research Centre, India:


Pulmonary TB Immune response ATT Immune responses in pulmonary tuberculosis Predictors for relapse

Additional relevant MeSH terms:


Tuberculosis Tuberculosis, Pulmonary Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections Moxifloxacin Fluoroquinolones Rifampin Isoniazid Pyrazinamide Ethambutol	Norgestimate, ethinyl estradiol drug combination Anti-Bacterial Agents Anti-Infective Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Contraceptives, Oral, Combined Contraceptives, Oral Contraceptive Agents, Female Contraceptive Agents Reproductive Control Agents Physiological Effects of Drugs Nucleic Acid Synthesis Inhibitors

Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Moxifloxacin
Fluoroquinolones
Rifampin
Isoniazid
Pyrazinamide
Ethambutol

Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors

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