Treatment of Latent Tuberculosis Infection With Isoniazid

May 25, 2010 updated by: Instituto Nacional de Salud Publica, Mexico

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Morelos
      • Cuernavaca, Morelos, Mexico, 62508
        • Instituto Nacional de Salud Publica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 85 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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
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
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Frequency of Mtb antigen-specific IFNγ-producing T cells measured by ELISPOT assay
Time Frame: 9 months
9 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Gene expression profiling
Time Frame: 9 months
9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Salud Publica, Mexico

Collaborators

Bill and Melinda Gates Foundation
Wellcome Trust

Investigators

  • Principal Investigator: Jose Sifuentes-Osornio, MD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  • Principal Investigator: Lourdes Garcia-Garcia, MD, Instituto Nacional de Salud Publica
  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2007

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

June 1, 2009

Study Registration Dates

First Submitted

February 16, 2006

First Submitted That Met QC Criteria

February 16, 2006

First Posted (Estimate)

February 17, 2006

Study Record Updates

Last Update Posted (Estimate)

May 26, 2010

Last Update Submitted That Met QC Criteria

May 25, 2010

Last Verified

May 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 137

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Tuberculosis

Clinical Trials on Isoniazid

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Moldova

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe