A Trial of Isoniazid for the Reversion of Interferon Gamma ELISPOT in Tuberculosis (TB) Case Contacts (IRS)
This study has been completed.
Sponsor:
Medical Research Council Unit, The Gambia
Information provided by:
Medical Research Council Unit, The Gambia
ClinicalTrials.gov Identifier:
NCT00130325
First received: August 11, 2005
Last updated: January 12, 2010
Last verified: January 2010
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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
U.S. FDA Resources
Further study details as provided by Medical Research Council Unit, The 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 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 |
More Information
Additional Information:
Publications:
| 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 Unit, The 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 June 13, 2013