TuberculosisPhase 4NCT00293228
Treatment of Latent Tuberculosis Infection With Isoniazid
A Phase 4 study testing Isoniazid in people with Tuberculosis, run by Instituto Nacional de Salud Publica, Mexico at 1 site in Mexico.
Trial summary
The purpose of this study is to study the effect that treatment of dormant tuberculosis infection has on the immunological system. We expect to observe an impact over the production of cytokines by peripheral white blood cells which may be useful to know if treatment has been effective. Read more about this study
- Who is it for?
- Ages 10 to 85 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Isoniazid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteMexico
- Study dates
- Feb 2007to Jun 2009
- Phase
- Phase 4
- 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 10 to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Informed consent
- Age 10-45
- Either sex
- Resident in study area
- Documented TST+ve (>10mm, Mantoux method, 2TU, PPD Statens Serum Institute)
- Normal chest radiograph
- HIV negative test
Who cannot join
- Active tuberculosis
- Previous diagnosis of tuberculosis
- Treatment for active or latent tuberculosis
- Contact with TB patients harboring MDR or INH resistant isolates of Mtb
- Diseases or therapies associated with immunosuppression
- Diabetes mellitus
Show all 12Show fewer
- Abnormal liver enzyme levels.
- HB below 8gr/dl
- Pregnancy (ascertained by urinary β-HCG)
- Allergy or intolerance to isoniazid
- Peripheral neuropathy
- Ingestion of drugs interacting with isoniazid
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Drugs for Treatment of Latent Tuberculosis Infection Objective 4: Identify Biomarkers for Clinical Trials of Drugs Active Against Latent TB
The purpose of this study is to study the effect that treatment of dormant tuberculosis infection has on the immunological system.
We expect to observe an impact over the production of cytokines by peripheral white blood cells which may be useful to know if treatment has been effective.
Read the detailed description
As part of on-going studies conducted in the Orizaba Health Jurisdiction in southeastern Mexico, household contacts of pulmonary TB patients who recently converted their tuberculin test and TST+ve contacts from randomly selected control households with no history of TB within the last 2 years (remote contacts) will be enrolled. We assume that these individuals are infected with Mycobacterium tuberculosis. Additional confidence that all subjects enrolled are latently infected will come from ELISPOT analysis of the response to ESAT-6 and CFP-10. We propose to administer INH to 100 TST+ve recent and 100 TST+ve remote contacts for 6 months. To control for spontaneous fluctuations of biomarker levels, we propose to defer therapy by 3 months to half the subjects in each group. Thus, four groups will be defined:
- Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.
- Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.
- Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.
- Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.
All contacts will undergo clinical evaluation at enrolment and review. The development of active TB will trigger withdrawal and full treatment. Fortnightly clinical review of group B during the deferred phase will be undertaken. ELISPOT analysis will be performed on all subjects at 0, 1, 4, 13, 26 and 40 weeks in groups A and C, and at 0, 13, 14, 17, 26, 40 and 54 weeks in groups B and D. A subset of 10 patients per group will be sampled for expression analysis at 0, 4, 26 and 40 weeks (groups A and C) and at 0, 13, 17 and 40 weeks in groups B and D (160 hybridizations in total).
- Conditions
- Tuberculosis
- Being tested
- Isoniazid
- Keywords
- Latent tuberculosis, biomarkers, isoniazid, ELISPOT, PPD positive individuals
- Medical subject headings
- Tuberculosis, Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsoniazidDrug
Also called treatment of latent tuberculosis infection
Isoniazid (5mg per kg up to 300 mg daily for 6 months)
isoniazidDrug
Also called Treatment of latent tuberculosis infection
isoniazid (5mg per kg up to 300 mg daily for 6 months
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment. Receives: Drug: Isoniazid |
| B | Active comparator | B. Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment. Receives: Drug: Isoniazid |
| C | Experimental | C. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment Receives: Drug: Isoniazid |
| D | Active comparator | D. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment. Receives: Drug: Isoniazid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Mtb antigen-specific IFNγ-producing T cells measured by ELISPOT assay
Measured: 9 months
Secondary outcomes (1)
Gene expression profiling
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2006 (estimated)
- Study startFeb 2007
- Primary completionMar 2008
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Salud Publica, Mexico
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Wellcome Trust
- Investigators
- Lourdes Garcia-Garcia, MD, Principal investigator, Instituto Nacional de Salud PúblicaJose Sifuentes-Osornio, MD, Principal investigator, Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranAlfredo Ponce-de-Leon, MD, Principal investigator, Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranEduardo Sada-Diaz, MD, Principal investigator, Instituto Nacional de Enfermedades RespiratoriasMartha Torres-Rojas, MD, Principal investigator, Instituto Nacional de Enfermedades Respiratorias
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00293228
- Sponsor's protocol ID
- 137
- Status last verified
- May 2010
- First submitted
- 16 Feb 2006
- Last updated
- 26 May 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wilkinson KA, Kon OM, Newton SM, Meintjes G, Davidson RN, Pasvol G, Wilkinson RJ. Effect of treatment of latent tuberculosis infection on the T cell response to Mycobacterium tuberculosis antigens. J Infect Dis. 2006 Feb 1;193(3):354-9. doi: 10.1086/499311. Epub 2005 Dec 29.
PubMed 16388482DeRiemer K, Garcia-Garcia L, Bobadilla-del-Valle M, Palacios-Martinez M, Martinez-Gamboa A, Small PM, Sifuentes-Osornio J, Ponce-de-Leon A. Does DOTS work in populations with drug-resistant tuberculosis? Lancet. 2005 Apr 2-8;365(9466):1239-45. doi: 10.1016/S0140-6736(05)74812-1.
PubMed 15811457Torres M, Garcia-Garcia L, Cruz-Hervert P, Guio H, Carranza C, Ferreyra-Reyes L, Canizales S, Molina S, Ferreira-Guerrero E, Tellez N, Montero-Campos R, Delgado-Sanchez G, Mongua-Rodriguez N, Sifuentes-Osornio J, Ponce-de Leon A, Sada E, Young DB, Wilkinson RJ. Effect of isoniazid on antigen-specific interferon-gamma secretion in latent tuberculosis. Eur Respir J. 2015 Feb;45(2):473-82. doi: 10.1183/09031936.00123314. Epub 2014 Oct 30.
PubMed 25359354
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Drugs for Treatment of Latent Tuberculosis Infection Objective 4: Identify Biomarkers for Clinical Trials of Drugs Active Against Latent TB
- ClinicalTrials.gov ID
- NCT00293228
- Acronym / sponsor ID
- 137
- Conditions
- Tuberculosis
- Keywords
- Latent tuberculosis, biomarkers, isoniazid, ELISPOT, PPD positive individuals
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Instituto Nacional de Salud Publica, MexicoUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Wellcome Trust
- Study start
- Feb 2007
- Primary completion
- Mar 2008 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 17 Feb 2006 (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.
The purpose of this study is to study the effect that treatment of dormant tuberculosis infection has on the immunological system.
We expect to observe an impact over the production of cytokines by peripheral white blood cells which may be useful to know if treatment has been effective.
Detailed description
As part of on-going studies conducted in the Orizaba Health Jurisdiction in southeastern Mexico, household contacts of pulmonary TB patients who recently converted their tuberculin test and TST+ve contacts from randomly selected control households with no history of TB within the last 2 years (remote contacts) will be enrolled. We assume that these individuals are infected with Mycobacterium tuberculosis. Additional confidence that all subjects enrolled are latently infected will come from ELISPOT analysis of the response to ESAT-6 and CFP-10. We propose to administer INH to 100 TST+ve recent and 100 TST+ve remote contacts for 6 months. To control for spontaneous fluctuations of biomarker levels, we propose to defer therapy by 3 months to half the subjects in each group. Thus, four groups will be defined:
- Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.
- Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.
- Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment.
- Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment.
All contacts will undergo clinical evaluation at enrolment and review. The development of active TB will trigger withdrawal and full treatment. Fortnightly clinical review of group B during the deferred phase will be undertaken. ELISPOT analysis will be performed on all subjects at 0, 1, 4, 13, 26 and 40 weeks in groups A and C, and at 0, 13, 14, 17, 26, 40 and 54 weeks in groups B and D. A subset of 10 patients per group will be sampled for expression analysis at 0, 4, 26 and 40 weeks (groups A and C) and at 0, 13, 17 and 40 weeks in groups B and D (160 hybridizations in total).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: IsoniazidRecently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment. |
| B | Active comparator | Drug: IsoniazidB. Recently converted contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment. |
| C | Experimental | Drug: IsoniazidC. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) immediately after recruitment |
| D | Active comparator | Drug: IsoniazidD. Remote contacts receiving isoniazid (5mg per kg up to 300 mg daily for 6 months) three months after recruitment. |
Who may qualify
- Ages
- 10 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Informed consent
- Age 10-45
- Either sex
- Resident in study area
- Documented TST+ve (>10mm, Mantoux method, 2TU, PPD Statens Serum Institute)
Key exclusion criteria (12 listed)
- Active tuberculosis
- Previous diagnosis of tuberculosis
- Treatment for active or latent tuberculosis
- Contact with TB patients harboring MDR or INH resistant isolates of Mtb
- Diseases or therapies associated with immunosuppression
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 |
|---|---|---|
| IsoniazidAlso: treatment of latent tuberculosis infectionIsoniazid (5mg per kg up to 300 mg daily for 6 months) | Drug | A, B, C, D |
| isoniazidAlso: Treatment of latent tuberculosis infectionisoniazid (5mg per kg up to 300 mg daily for 6 months | Drug | A, B, C, D |
Primary outcome
Frequency of Mtb antigen-specific IFNγ-producing T cells measured by ELISPOT assay
Time frame: 9 months
1 secondary outcome
Gene expression profiling
Time frame: 9 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 26 May 2010.
- Background: PubMed 16388482Wilkinson KA, Kon OM, Newton SM, Meintjes G, Davidson RN, Pasvol G, Wilkinson RJ. Effect of treatment of latent tuberculosis infection on the T cell response to Mycobacterium tuberculosis antigens. J Infect Dis. 2006 Feb 1;193(3):354-9. doi: 10.1086/499311. Epub 2005 Dec 29.
- Background: PubMed 15811457DeRiemer K, Garcia-Garcia L, Bobadilla-del-Valle M, Palacios-Martinez M, Martinez-Gamboa A, Small PM, Sifuentes-Osornio J, Ponce-de-Leon A. Does DOTS work in populations with drug-resistant tuberculosis? Lancet. 2005 Apr 2-8;365(9466):1239-45. doi: 10.1016/S0140-6736(05)74812-1.
- Derived from this study: PubMed 25359354Torres M, Garcia-Garcia L, Cruz-Hervert P, Guio H, Carranza C, Ferreyra-Reyes L, Canizales S, Molina S, Ferreira-Guerrero E, Tellez N, Montero-Campos R, Delgado-Sanchez G, Mongua-Rodriguez N, Sifuentes-Osornio J, Ponce-de Leon A, Sada E, Young DB, Wilkinson RJ. Effect of isoniazid on antigen-specific interferon-gamma secretion in latent tuberculosis. Eur Respir J. 2015 Feb;45(2):473-82. doi: 10.1183/09031936.00123314. Epub 2014 Oct 30.
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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.
Lourdes Garcia-Garcia, MD principal investigator
Instituto Nacional de Salud Pública
Jose Sifuentes-Osornio, MD principal investigator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Alfredo Ponce-de-Leon, MD principal investigator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Isoniazid in people with Tuberculosis, run by Instituto Nacional de Salud Publica, Mexico at 1 site in Mexico.
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 7 inclusion and 12 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 26 May 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 Mexico. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Frequency of Mtb antigen-specific IFNγ-producing T cells measured by ELISPOT assay (time frame: 9 months). 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 NCT00293228, which also lists 3 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 26 May 2010.