Treatment of Latent Tuberculosis Infection With Isoniazid

NCT ID: NCT00293228

Last Updated: 2010-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2009-06-30

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.

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).

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

A

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

Group Type: EXPERIMENTAL

Isoniazid

Intervention Type: DRUG

Isoniazid (5mg per kg up to 300 mg daily for 6 months)

isoniazid

Intervention Type: DRUG

isoniazid (5mg per kg up to 300 mg daily for 6 months

B

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

Group Type: ACTIVE_COMPARATOR

Isoniazid

Intervention Type: DRUG

Isoniazid (5mg per kg up to 300 mg daily for 6 months)

isoniazid

Intervention Type: DRUG

isoniazid (5mg per kg up to 300 mg daily for 6 months

C

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

Group Type: EXPERIMENTAL

Isoniazid

Intervention Type: DRUG

Isoniazid (5mg per kg up to 300 mg daily for 6 months)

isoniazid

Intervention Type: DRUG

isoniazid (5mg per kg up to 300 mg daily for 6 months

D

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

Group Type: ACTIVE_COMPARATOR

Isoniazid

Intervention Type: DRUG

Isoniazid (5mg per kg up to 300 mg daily for 6 months)

isoniazid

Intervention Type: DRUG

isoniazid (5mg per kg up to 300 mg daily for 6 months

Interventions

Isoniazid

Isoniazid (5mg per kg up to 300 mg daily for 6 months)

Intervention Type: DRUG

isoniazid

isoniazid (5mg per kg up to 300 mg daily for 6 months

Intervention Type: DRUG

Other Intervention Names

treatment of latent tuberculosis infection; Treatment of latent tuberculosis infection

Eligibility 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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bill and Melinda Gates Foundation

OTHER

Sponsor Role: collaborator

Wellcome Trust

OTHER

Sponsor Role: collaborator

Instituto Nacional de Salud Publica, Mexico

OTHER

Sponsor Role: lead

Responsible Party

Instituto Nacional de Salud Publica

Principal Investigators

Lourdes Garcia-Garcia, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Salud Pública

Jose Sifuentes-Osornio, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Alfredo Ponce-de-Leon, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Eduardo Sada-Diaz, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Enfermedades Respiratorias

Martha Torres-Rojas, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Enfermedades Respiratorias

Locations

Instituto Nacional de Salud Pública

Cuernavaca, Morelos, Mexico

Countries

Mexico

References

Wilkinson KA, Kon OM, Newton SM, Meintjes G, Davidson RN, Pasvol G, Wilkinson RJ. Effect of treatment of latent tuberculosis infection on the T cell response to Mycobacterium tuberculosis antigens. J Infect Dis. 2006 Feb 1;193(3):354-9. doi: 10.1086/499311. Epub 2005 Dec 29.

Reference Type: BACKGROUND

PMID: 16388482 (View on PubMed)

DeRiemer K, Garcia-Garcia L, Bobadilla-del-Valle M, Palacios-Martinez M, Martinez-Gamboa A, Small PM, Sifuentes-Osornio J, Ponce-de-Leon A. Does DOTS work in populations with drug-resistant tuberculosis? Lancet. 2005 Apr 2-8;365(9466):1239-45. doi: 10.1016/S0140-6736(05)74812-1.

Reference Type: BACKGROUND

PMID: 15811457 (View on PubMed)

Torres M, Garcia-Garcia L, Cruz-Hervert P, Guio H, Carranza C, Ferreyra-Reyes L, Canizales S, Molina S, Ferreira-Guerrero E, Tellez N, Montero-Campos R, Delgado-Sanchez G, Mongua-Rodriguez N, Sifuentes-Osornio J, Ponce-de Leon A, Sada E, Young DB, Wilkinson RJ. Effect of isoniazid on antigen-specific interferon-gamma secretion in latent tuberculosis. Eur Respir J. 2015 Feb;45(2):473-82. doi: 10.1183/09031936.00123314. Epub 2014 Oct 30.

Reference Type: DERIVED

PMID: 25359354 (View on PubMed)

Other Identifiers

137

Identifier Type: -

Identifier Source: org_study_id