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Treatment of Latent Tuberculosis Infection With Isoniazid

This study has been completed.
Sponsor:
Collaborators:
Bill and Melinda Gates Foundation
Wellcome Trust
Information provided by:
Instituto Nacional de Salud Publica, Mexico
ClinicalTrials.gov Identifier:
NCT00293228
First received: February 16, 2006
Last updated: May 25, 2010
Last verified: May 2010
History of Changes
  Purpose

The purpose of this study is to study the effect that treatment of dormant tuberculosis infection has on the immunological system.

We expect to observe an impact over the production of cytokines by peripheral white blood cells which may be useful to know if treatment has been effective.


Condition Intervention Phase
Tuberculosis
 Drug: Isoniazid
Drug: isoniazid
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Drugs for Treatment of Latent Tuberculosis Infection Objective 4: Identify Biomarkers for Clinical Trials of Drugs Active Against Latent TB

Resource links provided by NLM:

MedlinePlus related topics: Tuberculosis
Drug Information available for: Isoniazid
U.S. FDA Resources

Further study details as provided by Instituto Nacional de Salud Publica, Mexico:

Primary Outcome Measures:
  • Frequency of Mtb antigen-specific IFNγ-producing T cells measured by ELISPOT assay [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Gene expression profiling [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: February 2007
Study Completion Date: June 2009
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.
 Drug: Isoniazid
Isoniazid (5mg per kg up to 300 mg daily for 6 months)
Other Name: treatment of latent tuberculosis infection
Drug: isoniazid
isoniazid (5mg per kg up to 300 mg daily for 6 months
Other Name: Treatment of latent tuberculosis infection
Active Comparator: B
B. Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.
 Drug: Isoniazid
Isoniazid (5mg per kg up to 300 mg daily for 6 months)
Other Name: treatment of latent tuberculosis infection
Drug: isoniazid
isoniazid (5mg per kg up to 300 mg daily for 6 months
Other Name: Treatment of latent tuberculosis infection
Experimental: C
C. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment
 Drug: Isoniazid
Isoniazid (5mg per kg up to 300 mg daily for 6 months)
Other Name: treatment of latent tuberculosis infection
Drug: isoniazid
isoniazid (5mg per kg up to 300 mg daily for 6 months
Other Name: Treatment of latent tuberculosis infection
Active Comparator: D
D. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.
 Drug: Isoniazid
Isoniazid (5mg per kg up to 300 mg daily for 6 months)
Other Name: treatment of latent tuberculosis infection
Drug: isoniazid
isoniazid (5mg per kg up to 300 mg daily for 6 months
Other Name: Treatment of latent tuberculosis infection

Detailed Description:

As part of on-going studies conducted in the Orizaba Health Jurisdiction in southeastern Mexico, household contacts of pulmonary TB patients who recently converted their tuberculin test and TST+ve contacts from randomly selected control households with no history of TB within the last 2 years (remote contacts) will be enrolled. We assume that these individuals are infected with Mycobacterium tuberculosis. Additional confidence that all subjects enrolled are latently infected will come from ELISPOT analysis of the response to ESAT-6 and CFP-10. We propose to administer INH to 100 TST+ve recent and 100 TST+ve remote contacts for 6 months. To control for spontaneous fluctuations of biomarker levels, we propose to defer therapy by 3 months to half the subjects in each group. Thus, four groups will be defined:

A. Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.

B. Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.

C. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.

D. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.

All contacts will undergo clinical evaluation at enrolment and review. The development of active TB will trigger withdrawal and full treatment. Fortnightly clinical review of group B during the deferred phase will be undertaken. ELISPOT analysis will be performed on all subjects at 0, 1, 4, 13, 26 and 40 weeks in groups A and C, and at 0, 13, 14, 17, 26, 40 and 54 weeks in groups B and D. A subset of 10 patients per group will be sampled for expression analysis at 0, 4, 26 and 40 weeks (groups A and C) and at 0, 13, 17 and 40 weeks in groups B and D (160 hybridizations in total).

  Eligibility

Ages Eligible for Study:   10 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Informed consent
  • Age 10-45
  • Either sex
  • Resident in study area
  • Documented TST+ve (>10mm, Mantoux method, 2TU, PPD Statens Serum Institute)
  • Normal chest radiograph
  • HIV negative test

Exclusion criteria:

  • Active tuberculosis
  • Previous diagnosis of tuberculosis
  • Treatment for active or latent tuberculosis
  • Contact with TB patients harboring MDR or INH resistant isolates of Mtb
  • Diseases or therapies associated with immunosuppression
  • Diabetes mellitus
  • Abnormal liver enzyme levels.
  • HB below 8gr/dl
  • Pregnancy (ascertained by urinary β-HCG)
  • Allergy or intolerance to isoniazid
  • Peripheral neuropathy
  • Ingestion of drugs interacting with isoniazid
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00293228

Locations
Mexico
Instituto Nacional de Salud Pública
Cuernavaca, Morelos, Mexico, 62508
Sponsors and Collaborators
Instituto Nacional de Salud Publica, Mexico
Bill and Melinda Gates Foundation
Wellcome Trust
Investigators
Principal Investigator: Lourdes Garcia-Garcia, MD Instituto Nacional de Salud Pública
Principal Investigator: Jose Sifuentes-Osornio, MD Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Principal Investigator: Alfredo Ponce-de-Leon, MD Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Principal Investigator: Eduardo Sada-Diaz, MD Instituto Nacional de Enfermedades Respiratorias
Principal Investigator: Martha Torres-Rojas, MD Instituto Nacional de Enfermedades Respiratorias
  More Information

Publications:

Responsible Party: Lourdes Garcia-Garcia, Instituto Nacional de Salud Publica
ClinicalTrials.gov Identifier: NCT00293228     History of Changes
Other Study ID Numbers: 137
Study First Received: February 16, 2006
Last Updated: May 25, 2010
Health Authority: Mexico: National Institute of Public Health, Health Secretariat

Keywords provided by Instituto Nacional de Salud Publica, Mexico:
Latent tuberculosis
biomarkers
isoniazid
ELISPOT
PPD positive individuals

Additional relevant MeSH terms:
Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Isoniazid
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
 Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Lipid Regulating Agents

ClinicalTrials.gov processed this record on May 23, 2013