Treatment of Latent Tuberculosis Infection With Isoniazid

Sponsor

Instituto Nacional de Salud Publica, Mexico (Other)

Overall Status

Completed

CT.gov ID

NCT00293228

Collaborator

Bill and Melinda Gates Foundation (Other), Wellcome Trust (Other)

200

Enrollment

Location

Arms

Duration (Months)

7.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Tuberculosis	Drug: Isoniazid Drug: isoniazid	Phase 4

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:

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

Mar 1, 2008

Actual Study Completion Date :

Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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 Names: treatment of latent tuberculosis infection Drug: isoniazid isoniazid (5mg per kg up to 300 mg daily for 6 months Other Names: 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 Names: treatment of latent tuberculosis infection Drug: isoniazid isoniazid (5mg per kg up to 300 mg daily for 6 months Other Names: 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 Names: treatment of latent tuberculosis infection Drug: isoniazid isoniazid (5mg per kg up to 300 mg daily for 6 months Other Names: 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 Names: treatment of latent tuberculosis infection Drug: isoniazid isoniazid (5mg per kg up to 300 mg daily for 6 months Other Names: Treatment of latent tuberculosis infection

Outcome Measures

Primary Outcome Measures

Frequency of Mtb antigen-specific IFNγ-producing T cells measured by ELISPOT assay [9 months]

Secondary Outcome Measures

Gene expression profiling [9 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	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