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

Tuberculosis Clinical Trial

— IRS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00130325
• Other study ID #: IRS SCC965
• Status: Completed
• Phase: N/A
• First received: August 11, 2005
• Last updated: January 12, 2010
• Start date: October 2004
• Est. completion date: June 2009

Study information

• Verified date: January 2010
• Source: Medical Research Council Unit, The Gambia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Gambia: Department of State for Health and Social Welfare
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: June 2009
• Est. primary completion date: October 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 15 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• Isoniazid
Isoniazid 900mg, tablets, twice a week for 6 months
• Isoniazid
INH 900mg twice weekly for 6 months
• Placebo of Isoniazid tablets 300mg
Isoniazid BP 0mg twice weekly for 6 months

Locations

Country	Name	City	State
Gambia	MRC Laboratories	Banjul	Ksmd

Sponsors (1)

Lead Sponsor	Collaborator
Medical Research Council Unit, The Gambia

Country where clinical trial is conducted

Gambia, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Qualitative IFN-g ELISPOT reversion		12 months	No
Primary	Quantitative IFN-g ELISPOT reversion		12 months	No

External Links

•   MRC laboratories, Gambia website