A Trial of Isoniazid for the Reversion of Interferon Gamma ELISPOT in Tuberculosis (TB) Case Contacts
Information source: Medical Research Council Unit, The Gambia
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Tuberculosis
Intervention: Isoniazid (Drug); Isoniazid (Drug); Placebo of Isoniazid tablets 300mg (Drug)
Phase: N/A
Status: Completed
Sponsored by: Medical Research Council Unit, The Gambia Official(s) and/or principal investigator(s): Philip C Hill, MPH FRACP, Principal Investigator, Affiliation: MRC Laboratories, Gambia Roger H Brookes, PhD, Principal Investigator, Affiliation: MRC laboratories, Gambia Richard A Adegbola, PhD FRCPath, Study Chair, Affiliation: MRC laboratories, Gambia
Summary
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.
Clinical Details
Official title: A Double Blind Placebo-controlled Randomized Trial of Isoniazid for the Reversion of a Positive IFNg ELISPOT in TB Case Contacts
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Qualitative IFN-g ELISPOT reversionQuantitative IFN-g ELISPOT reversion
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
Minimum age: 15 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
MRC Laboratories, Banjul, Ksmd Po Box 273 Banjul, Gambia
Additional Information
MRC laboratories, Gambia website
Related 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.
Starting date: October 2004
Last updated: January 12, 2010
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