Treatment of Latent Tuberculosis Infection With Isoniazid

Tuberculosis Clinical Trial

Official title:

Drugs for Treatment of Latent Tuberculosis Infection Objective 4: Identify Biomarkers for Clinical Trials of Drugs Active Against Latent TB

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00293228
• Other study ID #: 137
• Status: Completed
• Phase: Phase 4
• First received: February 16, 2006
• Last updated: May 25, 2010
• Start date: February 2007
• Est. completion date: June 2009

Study information

• Verified date: May 2010
• Source: Instituto Nacional de Salud Publica, Mexico
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: June 2009
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 85 Years

Eligibility

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 ß-HCG)

• Allergy or intolerance to isoniazid

• Peripheral neuropathy

• Ingestion of drugs interacting with isoniazid

Related Conditions & MeSH terms

• Latent Tuberculosis
• Tuberculosis

Intervention

Drug:
• Isoniazid
Isoniazid (5mg per kg up to 300 mg daily for 6 months)
• isoniazid
isoniazid (5mg per kg up to 300 mg daily for 6 months

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Salud Pública	Cuernavaca	Morelos

Sponsors (3)

Lead Sponsor	Collaborator
Instituto Nacional de Salud Publica, Mexico	Bill and Melinda Gates Foundation, Wellcome Trust

Country where clinical trial is conducted

Mexico, 

References & Publications (2)

DeRiemer K, García-García L, Bobadilla-del-Valle M, Palacios-Martínez M, Martínez-Gamboa A, Small PM, Sifuentes-Osornio J, Ponce-de-León A. Does DOTS work in populations with drug-resistant tuberculosis? Lancet. 2005 Apr 2-8;365(9466):1239-45. — View Citation

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. Epub 2005 Dec 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Mtb antigen-specific IFN?-producing T cells measured by ELISPOT assay		9 months
Secondary	Gene expression profiling		9 months