A Trial of Isoniazid for the Reversion of Interferon Gamma ELISPOT in Tuberculosis (TB) Case Contacts (IRS)

January 12, 2010 updated by: Medical Research Council Unit, The Gambia

A Double Blind Placebo-controlled Randomized Trial of Isoniazid for the Reversion of a Positive IFNg ELISPOT in TB Case Contacts

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

214

Phase

  • Not Applicable

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

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

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

15 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

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: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Qualitative IFN-g ELISPOT reversion
Time Frame: 12 months
12 months
Quantitative IFN-g ELISPOT reversion
Time Frame: 12 months
12 months

Collaborators and Investigators

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

Sponsor

Medical Research Council Unit, The 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

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

Helpful Links

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

October 1, 2004

Primary Completion (ACTUAL)

October 1, 2008

Study Completion (ACTUAL)

June 1, 2009

Study Registration Dates

First Submitted

August 11, 2005

First Submitted That Met QC Criteria

August 11, 2005

First Posted (ESTIMATE)

August 15, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

January 13, 2010

Last Update Submitted That Met QC Criteria

January 12, 2010

Last Verified

January 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRS SCC965

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.

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