Mycobacterium TuberculosisNCT00340990
Immune Responses to Mycobacterium Tuberculosis
An observational study of Mycobacterium Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
Trial summary
This study, conducted at the University of Mali in the capital city of Bamako, will investigate how the body reacts to infection with Mycobacterium tuberculosis (MTB), the organism that causes tuberculosis. Tuberculosis is a major global health problem whose solution requires development of an effective vaccine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mycobacterium Tuberculosis
- How many people
- 111 participants
- Where
- 1 siteMali
- Study dates
- 6 Oct 2003to 27 Nov 2015
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to sign informed consent and willingness to comply with study requirements (including storage of blood specimens for future research on HIV, AIDS, MTB or the immune system).
- CATEGORY-SPECIFIC MTB INCLUSION CRITERIA:
- Group A (HIV-/MTB[BCG]) HIV ELISA(2) negative; BCG vaccinated with TST(2) less than 15 mm
- Group B (HIV+/MTB[BCG]) HIV ELISA/WB(2) positive; BCG vaccinated with TST less than 5 mm
- Group C (HIV-/MTB[pulm]) HIV ELISA negative; pulmonary MTB
- Group D (HIV-/MTB[diss]) HIV ELISA negative; disseminated MTB
- Group E (HIV+/MTB[pulm]) HIV ELISA/WB positive; pulmonary MTB
- Group F (HIV+/MTB[diss]) HIV ELISA/WB positive; disseminated MTB
Who cannot join
- Age less than 18 years (because of the risk for inducing protocol-related anemia)
- Hg less than 7.5 g/dL
- Latent MTB infection (as evidenced by a TST greater than 5 mm if HIV infected or greater than 15 mm if HIV uninfected) for arms A and B only.
- Past history of treated MTB infection
- Known or underlying bleeding disorder (due to risk of bleeding from venipuncture)
- Psychiatric illness that might interfere with study compliance
- Use of immunomodulators (including corticosteroids and IL-2) or cytotoxic agents (including hydroxyurea) within 45 days of signing consent and at any time during study
- Small or difficult to access antecubital veins that make venipuncture difficult
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Study of CD4+ T Cell Immune Responses to Mycobacterium Tuberculosis
This study, conducted at the University of Mali in the capital city of Bamako, will investigate how the body reacts to infection with Mycobacterium tuberculosis (MTB), the organism that causes tuberculosis. Tuberculosis is a major global health problem whose solution requires development of an effective vaccine. However, incomplete understanding of how immunity to MTB is acquired and measured limits vaccine development. This study will focus on certain immune system cells - CD4+ T cells - that appear to be very important in fighting tuberculosis.
Individuals 16 years of age and older who have or have not been exposed to either tuberculosis or HIV, or both, may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests, review of medical records and laboratory tests, and, if medically indicated, a chest x-ray. Individuals whose medical records indicate a past history of tuberculosis or a positive test for exposure to tuberculosis will have a tuberculin skin test. For this test, a few drops of fluid are placed under the skin to see if the immune system reacts to the substance, indicating previous exposure to MTB.
Read more
Participants will come to the University of Mali 10 times over a 1-year period - 7 times within the first 3 months of the study and then once every 3 months until 1 year after enrollment. At each study visit, they will be asked about their medical history and will donate 75 milliliters (about 1/3 cup) of blood, totaling 830 mL over the entire year. More blood may be requested if the participant's immune system reacts strongly to MTB in laboratory tests. No more than 450 mL (2 cups) of blood would be collected every 6 weeks; this amount is the Red Cross limit for regular blood donations every 6 weeks.
The blood samples will be used for tests that measure the level of immunity to tuberculosis. Genetic tests may be performed on blood cells to help interpret special tests of immunity. Because HIV-infected people are included in the study, the findings may also provide information on how HIV renders vulnerability to opportunistic infections, including tuberculosis.
Read the detailed description
Tuberculosis is a daunting global health problem. The solution requires development of an effective vaccine. But incomplete understanding of Mycobacterium tuberculosis (MTB) immunity-how it is acquired, how it is measured-limits vaccine development to empiric rather than rational approaches. New perspectives are needed. Most individuals infected with MTB never actually develop active tuberculosis. Similarly, most individuals with treated tuberculosis or BCG vaccination are also protected from subsequent disease. These individuals may be said to be immune. One approach to obtaining greater understanding of MTB immunity is to study these individuals to discover mechanisms of immunity that mediate their protection from disease. Because it is already known that CD4+ T cells are a critical component of MTB immunity, studying CD4+ T cell responses to MTB infection in immune individuals is a reasonable starting point. To determine which CD4+ T cell subsets and which CD4+ T cell immune responses are important, we will compare individuals with prior exposure (immunity) to MTB to individuals with active tuberculosis. Because HIV infection interferes with the CD4+ T cell response to MTB, it dramatically increases the risks for acquiring MTB infection and for developing disease. Under these circumstances it is easier to discern mechanisms relevant to MTB immunity because of exaggerated MTB-specific responses. In this study we aim to identify CD4+ T cell subsets and responses that correlate with MTB immunity. We anticipate that these correlations will yield new insight into mechanisms of MTB immunity that will be relevant to vaccine development. In addition, by examining MTB immunity in the setting of HIV coinfection, we anticipate new insights into mechanisms of how HIV causes disease.
- Conditions
- Mycobacterium Tuberculosis
- Keywords
- Tuberculosis, HIV, CD4+ T Cell, Interferon-Gamma, Lymphocyte Proliferation
- Medical subject headings
- Tuberculosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start6 Oct 2003
- Study completion27 Nov 2015
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 Mycobacterium TuberculosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Observational
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sophia B Siddiqui, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00340990
- Sponsor's protocol ID
- 999904009
- Other IDs
- 04-I-N009
- Status last verified
- 27 Nov 2015
- First submitted
- 19 Jun 2006
- Last updated
- 5 Dec 2019
- Results posted
- No
Publications
Ellner JJ. Review: the immune response in human tuberculosis--implications for tuberculosis control. J Infect Dis. 1997 Nov;176(5):1351-9. doi: 10.1086/514132. No abstract available.
PubMed 9359738Orme IM, Andersen P, Boom WH. T cell response to Mycobacterium tuberculosis. J Infect Dis. 1993 Jun;167(6):1481-97. doi: 10.1093/infdis/167.6.1481.
PubMed 8501346Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999 Oct 14;401(6754):708-12. doi: 10.1038/44385.
PubMed 10537110
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of CD4+ T Cell Immune Responses to Mycobacterium Tuberculosis
- ClinicalTrials.gov ID
- NCT00340990
- Acronym / sponsor ID
- 999904009
- Conditions
- Mycobacterium Tuberculosis
- Keywords
- Tuberculosis, HIV, CD4+ T Cell, Interferon-Gamma, Lymphocyte Proliferation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 111 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 6 Oct 2003
- Study completion
- 27 Nov 2015
- First posted
- 21 Jun 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.
This study, conducted at the University of Mali in the capital city of Bamako, will investigate how the body reacts to infection with Mycobacterium tuberculosis (MTB), the organism that causes tuberculosis. Tuberculosis is a major global health problem whose solution requires development of an effective vaccine. However, incomplete understanding of how immunity to MTB is acquired and measured limits vaccine development. This study will focus on certain immune system cells - CD4+ T cells - that appear to be very important in fighting tuberculosis.
Individuals 16 years of age and older who have or have not been exposed to either tuberculosis or HIV, or both, may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests, review of medical records and laboratory tests, and, if medically indicated, a chest x-ray. Individuals whose medical records indicate a past history of tuberculosis or a positive test for exposure to tuberculosis will have a tuberculin skin test. For this test, a few drops of fluid are placed under the skin to see if the immune system reacts to the substance, indicating previous exposure to MTB.
Participants will come to the University of Mali 10 times over a 1-year period - 7 times within the first 3 months of the study and then once every 3 months until 1 year after enrollment. At each study visit, they will be asked about their medical history and will donate 75 milliliters (about 1/3 cup) of blood, totaling 830 mL over the entire year. More blood may be requested if the participant's immune system reacts strongly to MTB in laboratory tests. No more than 450 mL (2 cups) of blood would be collected every 6 weeks; this amount is the Red Cross limit for regular blood donations every 6 weeks.
The blood samples will be used for tests that measure the level of immunity to tuberculosis. Genetic tests may be performed on blood cells to help interpret special tests of immunity. Because HIV-infected people are included in the study, the findings may also provide information on how HIV renders vulnerability to opportunistic infections, including tuberculosis.
Detailed description
Tuberculosis is a daunting global health problem. The solution requires development of an effective vaccine. But incomplete understanding of Mycobacterium tuberculosis (MTB) immunity-how it is acquired, how it is measured-limits vaccine development to empiric rather than rational approaches. New perspectives are needed. Most individuals infected with MTB never actually develop active tuberculosis. Similarly, most individuals with treated tuberculosis or BCG vaccination are also protected from subsequent disease. These individuals may be said to be immune. One approach to obtaining greater understanding of MTB immunity is to study these individuals to discover mechanisms of immunity that mediate their protection from disease. Because it is already known that CD4+ T cells are a critical component of MTB immunity, studying CD4+ T cell responses to MTB infection in immune individuals is a reasonable starting point. To determine which CD4+ T cell subsets and which CD4+ T cell immune responses are important, we will compare individuals with prior exposure (immunity) to MTB to individuals with active tuberculosis. Because HIV infection interferes with the CD4+ T cell response to MTB, it dramatically increases the risks for acquiring MTB infection and for developing disease. Under these circumstances it is easier to discern mechanisms relevant to MTB immunity because of exaggerated MTB-specific responses. In this study we aim to identify CD4+ T cell subsets and responses that correlate with MTB immunity. We anticipate that these correlations will yield new insight into mechanisms of MTB immunity that will be relevant to vaccine development. In addition, by examining MTB immunity in the setting of HIV coinfection, we anticipate new insights into mechanisms of how HIV causes disease.
Study design
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Ability to sign informed consent and willingness to comply with study requirements (including storage of blood specimens for future research on HIV, AIDS, MTB or the immune system).
- Group A (HIV-/MTB[BCG]) HIV ELISA(2) negative; BCG vaccinated with TST(2) less than 15 mm
- Group B (HIV+/MTB[BCG]) HIV ELISA/WB(2) positive; BCG vaccinated with TST less than 5 mm
- Group C (HIV-/MTB[pulm]) HIV ELISA negative; pulmonary MTB
- Group D (HIV-/MTB[diss]) HIV ELISA negative; disseminated MTB
Key exclusion criteria (8 listed)
- Age less than 18 years (because of the risk for inducing protocol-related anemia)
- Hg less than 7.5 g/dL
- Latent MTB infection (as evidenced by a TST greater than 5 mm if HIV infected or greater than 15 mm if HIV uninfected) for arms A and B only.
- Past history of treated MTB infection
- Known or underlying bleeding disorder (due to risk of bleeding from venipuncture)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 5 Dec 2019.
- Background: PubMed 9359738Ellner JJ. Review: the immune response in human tuberculosis--implications for tuberculosis control. J Infect Dis. 1997 Nov;176(5):1351-9. doi: 10.1086/514132. No abstract available.
- Background: PubMed 8501346Orme IM, Andersen P, Boom WH. T cell response to Mycobacterium tuberculosis. J Infect Dis. 1993 Jun;167(6):1481-97. doi: 10.1093/infdis/167.6.1481.
- Background: PubMed 10537110Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999 Oct 14;401(6754):708-12. doi: 10.1038/44385.
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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.
Sophia B Siddiqui, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mycobacterium Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
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 8 inclusion and 8 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 5 Dec 2019. 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 Mali. 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.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00340990, 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 5 Dec 2019.