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

NCT ID: NCT00130325

Last Updated: 2010-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31
• Study Completion Date: 2009-06-30

Brief 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.

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.

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

A

Isoniazid arm

Group Type: ACTIVE_COMPARATOR

Isoniazid

Intervention Type: DRUG

Isoniazid 900mg, tablets, twice a week for 6 months

Isoniazid

Intervention Type: DRUG

INH 900mg twice weekly for 6 months

B

Placebo of Isoniazid tablet 300mg

Group Type: PLACEBO_COMPARATOR

Placebo of Isoniazid tablets 300mg

Intervention Type: DRUG

Isoniazid BP 0mg twice weekly for 6 months

Interventions

Isoniazid

Isoniazid 900mg, tablets, twice a week for 6 months

Intervention Type: DRUG

Isoniazid

INH 900mg twice weekly for 6 months

Intervention Type: DRUG

Placebo of Isoniazid tablets 300mg

Isoniazid BP 0mg twice weekly for 6 months

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical Research Council Unit, The Gambia

OTHER

Sponsor Role: lead

Responsible Party

MRC (UK) Laboratories, The Gambia

Principal Investigators

Philip C Hill, MPH FRACP

Role: PRINCIPAL_INVESTIGATOR

MRC Laboratories, Gambia

Roger H Brookes, PhD

Role: PRINCIPAL_INVESTIGATOR

MRC laboratories, Gambia

Richard A Adegbola, PhD FRCPath

Role: STUDY_CHAIR

MRC laboratories, Gambia

Locations

MRC Laboratories

Banjul, KSMD, The Gambia

Countries

The Gambia

References

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. doi: 10.1086/382362. Epub 2004 Mar 16.

Reference Type: BACKGROUND

PMID: 15034828 (View on PubMed)

Adetifa IM, Ota MO, Jeffries DJ, Lugos MD, Hammond AS, Battersby NJ, Owiafe PK, Donkor SD, Antonio M, Ibanga HB, Brookes RH, Aka P, Walton R, Adegbola RA, Hill PC. Interferon-gamma ELISPOT as a biomarker of treatment efficacy in latent tuberculosis infection: a clinical trial. Am J Respir Crit Care Med. 2013 Feb 15;187(4):439-45. doi: 10.1164/rccm.201208-1352OC. Epub 2012 Dec 6.

Reference Type: DERIVED

PMID: 23220919 (View on PubMed)

Other Identifiers

IRS SCC965

Identifier Type: -

Identifier Source: org_study_id