search
Back to results

Treatment of Latent Tuberculosis Infection With Isoniazid

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 4
Locations
Mexico
Study Type
Interventional
Intervention
Isoniazid
isoniazid
Sponsored by
Instituto Nacional de Salud Publica, Mexico
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Tuberculosis focused on measuring Latent tuberculosis, biomarkers, isoniazid, ELISPOT, PPD positive individuals

Eligibility Criteria

10 Years - 85 Years (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Instituto Nacional de Salud Pública

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

A

B

C

D

Arm Description

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.

Outcomes

Primary Outcome Measures

Frequency of Mtb antigen-specific IFNγ-producing T cells measured by ELISPOT assay

Secondary Outcome Measures

Gene expression profiling

Full Information

First Posted
February 16, 2006
Last Updated
May 25, 2010
Sponsor
Instituto Nacional de Salud Publica, Mexico
Collaborators
Bill and Melinda Gates Foundation, Wellcome Trust
search

1. Study Identification

Unique Protocol Identification Number
NCT00293228
Brief Title
Treatment of Latent Tuberculosis Infection With Isoniazid
Official Title
Drugs for Treatment of Latent Tuberculosis Infection Objective 4: Identify Biomarkers for Clinical Trials of Drugs Active Against Latent TB
Study Type
Interventional

2. Study Status

Record Verification Date
May 2010
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Instituto Nacional de Salud Publica, Mexico
Collaborators
Bill and Melinda Gates Foundation, Wellcome Trust

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
Latent tuberculosis, biomarkers, isoniazid, ELISPOT, PPD positive individuals

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.
Arm Title
B
Arm Type
Active Comparator
Arm Description
B. Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.
Arm Title
C
Arm Type
Experimental
Arm Description
C. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment
Arm Title
D
Arm Type
Active Comparator
Arm Description
D. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.
Intervention Type
Drug
Intervention Name(s)
Isoniazid
Other Intervention Name(s)
treatment of latent tuberculosis infection
Intervention Description
Isoniazid (5mg per kg up to 300 mg daily for 6 months)
Intervention Type
Drug
Intervention Name(s)
isoniazid
Other Intervention Name(s)
Treatment of latent tuberculosis infection
Intervention Description
isoniazid (5mg per kg up to 300 mg daily for 6 months
Primary Outcome Measure Information:
Title
Frequency of Mtb antigen-specific IFNγ-producing T cells measured by ELISPOT assay
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Gene expression profiling
Time Frame
9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lourdes Garcia-Garcia, MD
Organizational Affiliation
Instituto Nacional de Salud Pública
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jose Sifuentes-Osornio, MD
Organizational Affiliation
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alfredo Ponce-de-Leon, MD
Organizational Affiliation
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eduardo Sada-Diaz, MD
Organizational Affiliation
Instituto Nacional de Enfermedades Respiratorias
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Martha Torres-Rojas, MD
Organizational Affiliation
Instituto Nacional de Enfermedades Respiratorias
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto Nacional de Salud Pública
City
Cuernavaca
State/Province
Morelos
ZIP/Postal Code
62508
Country
Mexico

12. IPD Sharing Statement

Citations:
PubMed Identifier
16388482
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. doi: 10.1086/499311. Epub 2005 Dec 29.
Results Reference
background
PubMed Identifier
15811457
Citation
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.
Results Reference
background
PubMed Identifier
25359354
Citation
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.
Results Reference
derived

Learn more about this trial

Treatment of Latent Tuberculosis Infection With Isoniazid

We'll reach out to this number within 24 hrs