A Trial of Isoniazid for the Reversion of Interferon Gamma ELISPOT in Tuberculosis (TB) Case Contacts - Full Text View

Sponsor:	Medical Research Council Laboratories, Gambia
Information provided by:	Medical Research Council Laboratories, Gambia
ClinicalTrials.gov Identifier:	NCT00130325

Purpose

There are new TB vaccines already developed that need to be tried in humans to assess their efficacy.

The researchers had previously shown that production of interferon gamma by T cells in response to TB antigens is a more specific marker of TB infection.

The researchers hypothesize that this can be used as a reliable early marker of TB vaccine efficacy. The researchers expect to show a significantly increased reversion of this test in household contacts of TB patients given Isoniazid prophylaxis treatment for 6 months.

Condition	Intervention
Tuberculosis	Drug: Isoniazid Drug: Placebo of Isoniazid tablets 300mg

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Double Blind Placebo-controlled Randomized Trial of Isoniazid for the Reversion of a Positive IFNg ELISPOT in TB Case Contacts

Resource links provided by NLM:

MedlinePlus related topics: Tuberculosis

Drug Information available for: Isoniazid Ftivazide

U.S. FDA Resources

Further study details as provided by Medical Research Council Laboratories, Gambia:

Primary Outcome Measures:

Qualitative IFN-g ELISPOT reversion [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Quantitative IFN-g ELISPOT reversion [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment:	214
Study Start Date:	October 2004
Study Completion Date:	June 2009
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: A Isoniazid arm	Drug: Isoniazid Isoniazid 900mg, tablets, twice a week for 6 months Drug: Isoniazid INH 900mg twice weekly for 6 months
Placebo Comparator: B Placebo of Isoniazid tablet 300mg	Drug: Placebo of Isoniazid tablets 300mg Isoniazid BP 0mg twice weekly for 6 months

Detailed Description:

Current efforts to control the spread of tuberculosis are failing. An increasingly large number of new generation vaccines are being produced and a plan for assessing their ability to prevent disease and treat infection needs to be developed.

The MRC Labs in The Gambia is well positioned to conduct safety and immunogenicity studies and also to conduct trials of the therapeutic effect of these vaccines in preventing disease in case contacts who are infected.

This study is part one of a three-step plan to develop a reliable early surrogate marker of the therapeutic efficacy of new TB vaccines.

The three-step plan is as follows:

Evaluate the ability of isoniazid, known to be effective in the treatment of MTB infection, to revert the antigen-specific IFNg-ELISPOT in ESAT-6 and/or CFP-10 positive contacts of TB patients.
Compare the ability of different combinations of a TB vaccine and isoniazid to revert the ELISPOT in a 4-arm randomised trial using:1) isoniazid alone, 2) a TB vaccine alone, 3) a combination of isoniazid and TB vaccine, and 4) placebo
Compare, in a randomized trial, the ability of TB vaccine or vaccine plus isoniazid versus isoniazid alone to prevent the development of secondary disease.

For this first step the researchers will test the following hypothesis:

Those receiving isoniazid have a significantly higher reversion rate of MTB-specific responses as measured with IFNg-ELISPOT assays compared to those who receive a placebo.

Eligibility

Ages Eligible for Study:	15 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy person aged 15 years and above
Normal medical history and physical examination
Normal biochemistry and haematological indices
Mantoux ≥ 10mm
Negative HIV antibody test
No serological evidence of hepatitis B virus (HBV) infection
Normal Chest X-ray
ESAT6 and/or CFP-10 peptides and ESAT6/CFP-10 protein positive (≥10 SFC for ESAT 6 or CFP-10 and ESAT6/CFP-10 protein).
Index case is sputum smear positive
Index case has chest X ray (CXR) characteristics of TB

Exclusion Criteria:

Pregnant female
Haemoglobin <8 g/dl
Previous history of tuberculosis
Clinical case of tuberculosis
Current participation in another clinical trial, or within 12 weeks of this study.
Any other factor that might increase the risk of an adverse outcome from participation in the trial
Significant history or evidence of skin disorder, allergy, immunodeficiency, organ specific disorders causing significant immunodeficiency.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00130325

Locations

Gambia
MRC Laboratories
Banjul, Ksmd, Gambia, Po Box 273 Banjul

Sponsors and Collaborators

Medical Research Council Laboratories, Gambia

Investigators

Principal Investigator:	Philip C Hill, MPH FRACP	MRC Laboratories, Gambia
Principal Investigator:	Roger H Brookes, PhD	MRC laboratories, Gambia
Study Chair:	Richard A Adegbola, PhD FRCPath	MRC laboratories, Gambia

More Information

Additional Information:

MRC laboratories, Gambia website This link exits the ClinicalTrials.gov site

Publications:

Hill PC, Brookes RH, Fox A, Fielding K, Jeffries DJ, Jackson-Sillah D, Lugos MD, Owiafe PK, Donkor SA, Hammond AS, Otu JK, Corrah T, Adegbola RA, McAdam KP. Large-scale evaluation of enzyme-linked immunospot assay and skin test for diagnosis of Mycobacterium tuberculosis infection against a gradient of exposure in The Gambia. Clin Infect Dis. 2004 Apr 1;38(7):966-73. Epub 2004 Mar 16.

Responsible Party:	Prof. Tumani Corrah, Unit Director, MRC (UK) Laboratories, The Gambia
ClinicalTrials.gov Identifier:	NCT00130325 History of Changes
Other Study ID Numbers:	IRS SCC965
Study First Received:	August 11, 2005
Last Updated:	January 12, 2010
Health Authority:	Gambia: Department of State for Health and Social Welfare

Keywords provided by Medical Research Council Laboratories, Gambia:

ELISPOT,
tuberculosis,
Mycobacterium tuberculosis
Isoniazid
Clinical trial

Additional relevant MeSH terms:

Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Isoniazid
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Lipid Regulating Agents

ClinicalTrials.gov processed this record on February 09, 2012