TuberculosisIRSNCT00130325
A Trial of Isoniazid for the Reversion of Interferon Gamma ELISPOT in Tuberculosis (TB) Case Contacts
A study testing Isoniazid in people with Tuberculosis, run by Medical Research Council Unit, The Gambia at 1 site in The Gambia.
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. Read more about this study
- Who is it for?
- Ages 15 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Isoniazid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 214 participants
- Where
- 1 siteThe Gambia
- Study dates
- Oct 2004to Jun 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Being tested
- Isoniazid, Placebo of Isoniazid tablets 300mg
- Keywords
- ELISPOT,, tuberculosis,, Mycobacterium tuberculosis, Isoniazid, Clinical trial
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsoniazidDrug
Isoniazid 900mg, tablets, twice a week for 6 months
IsoniazidDrug
INH 900mg twice weekly for 6 months
Placebo of Isoniazid tablets 300mgDrug
Isoniazid BP 0mg twice weekly for 6 months
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Isoniazid arm Receives: Drug: Isoniazid |
| B | Placebo comparator | Placebo of Isoniazid tablet 300mg Receives: Drug: Placebo of Isoniazid tablets 300mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Qualitative IFN-g ELISPOT reversion
Measured: 12 months
Quantitative IFN-g ELISPOT reversion
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2005 (estimated)
- Study startOct 2004
- Primary completionOct 2008
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 214 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical Research Council Unit, The Gambia
- Sponsor type
- University, hospital or other
- Investigators
- Philip C Hill, MPH FRACP, Principal investigator, MRC Laboratories, GambiaRoger H Brookes, PhD, Principal investigator, MRC laboratories, GambiaRichard A Adegbola, PhD FRCPath, Study chair, MRC laboratories, Gambia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00130325
- Sponsor's protocol ID
- IRS SCC965
- Acronym
- IRS
- Status last verified
- Jan 2010
- First submitted
- 11 Aug 2005
- Last updated
- 13 Jan 2010
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.1086/382362. Epub 2004 Mar 16.
PubMed 15034828Adetifa 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.
PubMed 23220919
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind Placebo-controlled Randomized Trial of Isoniazid for the Reversion of a Positive IFNg ELISPOT in TB Case Contacts
- ClinicalTrials.gov ID
- NCT00130325
- Acronym / sponsor ID
- IRS / IRS SCC965
- Conditions
- Tuberculosis
- Keywords
- ELISPOT,, tuberculosis,, Mycobacterium tuberculosis, Isoniazid, Clinical trial
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 214 participants (actual)
- Lead sponsor
- Medical Research Council Unit, The GambiaUniversity, hospital or other
- Study start
- Oct 2004
- Primary completion
- Oct 2008 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 15 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: IsoniazidIsoniazid arm |
| B | Placebo comparator | Drug: Placebo of Isoniazid tablets 300mgPlacebo of Isoniazid tablet 300mg |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Healthy person aged 15 years and above
- Normal medical history and physical examination
- Normal biochemistry and haematological indices
- Mantoux ≥ 10mm
- Negative HIV antibody test
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsoniazidIsoniazid 900mg, tablets, twice a week for 6 months | Drug | A |
| IsoniazidINH 900mg twice weekly for 6 months | Drug | A |
| Placebo of Isoniazid tablets 300mgIsoniazid BP 0mg twice weekly for 6 months | Drug | B |
Primary outcome
Qualitative IFN-g ELISPOT reversion
Time frame: 12 months
Quantitative IFN-g ELISPOT reversion
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2010.
- Background: PubMed 15034828Hill 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.
- Derived from this study: PubMed 23220919Adetifa 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.
- MRC laboratories, Gambia websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip C Hill, MPH FRACP principal investigator
MRC Laboratories, Gambia
Roger H Brookes, PhD principal investigator
MRC laboratories, Gambia
Richard A Adegbola, PhD FRCPath study chair
MRC laboratories, Gambia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Isoniazid in people with Tuberculosis, run by Medical Research Council Unit, The Gambia at 1 site in The Gambia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in The Gambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Qualitative IFN-g ELISPOT reversion (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00130325, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2010.