Latency in Pulmonary Tuberculosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2011 by Tuberculosis Research Centre, India
Sponsor:
Collaborator:
Information provided by:
Tuberculosis Research Centre, India
ClinicalTrials.gov Identifier:
NCT01154959
First received: June 30, 2010
Last updated: June 15, 2011
Last verified: June 2011
  Purpose

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 Intervention Phase
Pulmonary Tuberculosis
Drug: Moxifloxacin, Isoniazid, Rifampicin Pyrazinamide, Ethambutol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Characterization of Immune Responses in Treatment-induced Latency in Pulmonary Tuberculosis

Resource links provided by NLM:


Further study details as provided by Tuberculosis Research Centre, India:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determining the correlation of increase in regulatory factors with the development of relapse in treated TB patients. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: February 2010
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Investigators
Principal Investigator: Subash Babu, MBBS, PhD Tuberculosis Research Centre, India
  More Information

Publications:

Responsible Party: Dr. S. Subash Babu, Tuberculosis Research Centre (ICMR)
ClinicalTrials.gov Identifier: NCT01154959     History of Changes
Other Study ID Numbers: LTB01
Study First Received: June 30, 2010
Last Updated: June 15, 2011
Health Authority: India: Indian Council of Medical Research

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
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
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

ClinicalTrials.gov processed this record on September 16, 2014