Ignite Creation Date:
2024-05-05 @ 12:08 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00257907
Status:
COMPLETED
Last Update Posted:
2018-04-05
First Post:
2005-11-22
Brief Title:
Immune Response to Mycobacterium Tuberculosis Infection
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Correlation of the Precursor Frequency of CD4 Effector Memory T Cells With Induration Measured in the Tuberculin Skin Test TST
Status:
COMPLETED
Status Verified Date:
2016-02-24
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine how the immune system responds to infection with Mycobacterium tuberculosis bacteria bacteria that cause tuberculosis in order to better understand how the germ produces infection and how the immune response might work to control the infection
Only about one in 10 people infected by M tuberculosis become sick sometimes years or even decades after exposure It is not known why some people become sick and most do not but the immune system of people who never develop disease may be better able to control the bacteria This study will evaluate the latent form of M tuberculosis infection to further the understanding of the immune mechanisms - particularly the role of certain white blood cells - involved in the disease process
Healthy volunteers 18 years of age and older may be eligible for this study Candidates are screened with a medical history family history of medical conditions sexual history history of drug use physical examination and blood tests including a test for HIV People in Mali West Africa and in local health clinics in the United States may participate
At the start of the study participants have blood tests and a tuberculin skin test PPD test which indicates whether a person has been exposed to tuberculosis bacteria For the PPD a tiny amount of liquid containing dead tuberculosis antigen is put under the skin of the forearm with a needle The antigen cannot cause infection or disease
After 3 days participants have another blood test and the site of the tuberculin test is examined for swelling that would indicate a positive result Participants with a positive PPD have a chest x-ray to check for tuberculosis disease Those whose x-ray is also positive are withdrawn from the study and referred to their doctor for evaluation and treatment Those whose x-ray is negative return to the clinic within 3 weeks of the tuberculin test to give another blood sample
Participants whose PPD is negative have a second tuberculin test 10 to 21 days later and return 3 days after the test to determine if it is still negative or if it is positive Some people who are negative after the first test may test positive after the second procedure Those whose test is still negative end their participation in the study at that time Participants whose second PPD is positive have a chest x-ray as described above and those with a negative chest x-ray return in 3 weeks to donate one last blood sample
The purpose of the present study is to evaluate the latent form of this infection the prevalence of which worldwide exceeds that of active disease Our hypothesis is that in latent tuberculosis antigen specific effector memory CD4 T cells are responsible for the generation of clinically measurable delayed type hypersensitivity and that central memory CD4T cells are not directly involved in this process We base this idea on the assumption that latent tuberculosis is a state of antigen persistence and that effector memory T cells should be maintained as long as antigeninfection is present
We propose to conduct this study in Mali West Africa and local clinics in the US Tuberculosis affects 5931000002 individuals in Mali and most have been exposed to the disease Additionally it would be important to evaluate the same parameters locally as latent infection is one of the major factors for reactivation tuberculosis in this country Patients would be enrolled in 4 major groups HIV-TST- Group A HIV-TST Group B HIVTSTG roup C and HIVTST- Group D
To evaluate this hypothesis we plan to enroll between 100 - 300 patients over the course of 2 years from both countries Blood samples before and at predetermined time points after the application of Purified Protein Derivative PPD will be obtained to determine the fraction of CD4 T cells which produce interferon gamma in response to stimulation with PPD with a 16hr antigen stimulation assay Appropriate staining will be done to ascertain the phenotype as well as cytokine production Interferon gamma IFN gamma Interleukin 2 IL2 and Tumour Necrosis Factor TNF Additionally lymphocyte proliferation will be studied using 5-and-6-carboxyflouorescein diacetate succinimidyl ester CFSE
In conducting this study we hope to further the understanding of the immune mechanisms involved particularly mechanisms of T cell memory which would provide insights into TB and HIV pathogenesis We also believe that understanding these mechanisms could lead towards establishment of surrogates for immunity in TB vaccine studies which could enhance vaccine trial design It might also help in understanding better the immunological dynamics of tuberculosis co-infection in individuals with HIV infection
Only about one in 10 people infected by M tuberculosis become sick sometimes years or even decades after exposure It is not known why some people become sick and most do not but the immune system of people who never develop disease may be better able to control the bacteria This study will evaluate the latent form of M tuberculosis infection to further the understanding of the immune mechanisms - particularly the role of certain white blood cells - involved in the disease process
Healthy volunteers 18 years of age and older may be eligible for this study Candidates are screened with a medical history family history of medical conditions sexual history history of drug use physical examination and blood tests including a test for HIV People in Mali West Africa and in local health clinics in the United States may participate
At the start of the study participants have blood tests and a tuberculin skin test PPD test which indicates whether a person has been exposed to tuberculosis bacteria For the PPD a tiny amount of liquid containing dead tuberculosis antigen is put under the skin of the forearm with a needle The antigen cannot cause infection or disease
After 3 days participants have another blood test and the site of the tuberculin test is examined for swelling that would indicate a positive result Participants with a positive PPD have a chest x-ray to check for tuberculosis disease Those whose x-ray is also positive are withdrawn from the study and referred to their doctor for evaluation and treatment Those whose x-ray is negative return to the clinic within 3 weeks of the tuberculin test to give another blood sample
Participants whose PPD is negative have a second tuberculin test 10 to 21 days later and return 3 days after the test to determine if it is still negative or if it is positive Some people who are negative after the first test may test positive after the second procedure Those whose test is still negative end their participation in the study at that time Participants whose second PPD is positive have a chest x-ray as described above and those with a negative chest x-ray return in 3 weeks to donate one last blood sample
The purpose of the present study is to evaluate the latent form of this infection the prevalence of which worldwide exceeds that of active disease Our hypothesis is that in latent tuberculosis antigen specific effector memory CD4 T cells are responsible for the generation of clinically measurable delayed type hypersensitivity and that central memory CD4T cells are not directly involved in this process We base this idea on the assumption that latent tuberculosis is a state of antigen persistence and that effector memory T cells should be maintained as long as antigeninfection is present
We propose to conduct this study in Mali West Africa and local clinics in the US Tuberculosis affects 5931000002 individuals in Mali and most have been exposed to the disease Additionally it would be important to evaluate the same parameters locally as latent infection is one of the major factors for reactivation tuberculosis in this country Patients would be enrolled in 4 major groups HIV-TST- Group A HIV-TST Group B HIVTSTG roup C and HIVTST- Group D
To evaluate this hypothesis we plan to enroll between 100 - 300 patients over the course of 2 years from both countries Blood samples before and at predetermined time points after the application of Purified Protein Derivative PPD will be obtained to determine the fraction of CD4 T cells which produce interferon gamma in response to stimulation with PPD with a 16hr antigen stimulation assay Appropriate staining will be done to ascertain the phenotype as well as cytokine production Interferon gamma IFN gamma Interleukin 2 IL2 and Tumour Necrosis Factor TNF Additionally lymphocyte proliferation will be studied using 5-and-6-carboxyflouorescein diacetate succinimidyl ester CFSE
In conducting this study we hope to further the understanding of the immune mechanisms involved particularly mechanisms of T cell memory which would provide insights into TB and HIV pathogenesis We also believe that understanding these mechanisms could lead towards establishment of surrogates for immunity in TB vaccine studies which could enhance vaccine trial design It might also help in understanding better the immunological dynamics of tuberculosis co-infection in individuals with HIV infection
Detailed Description:
Tuberculosis TB is a major global health concern One third of the worlds population is infected with Mycobacterium tuberculosis Two to 3 million people die every year of the disease with 8-10 million new cases per year It is projected that there will be 90 million new cases and 30 million deaths over the next decade For a disease which we know to have existed since 2400 BC our understanding of its pathogenesis is incomplete especially in relation to the human immune response and the role of lymphocytes in particular
The purpose of the present study is to evaluate the latent form of this infection the prevalence of which worldwide exceeds that of active disease Our hypothesis is that in latent tuberculosis antigen specific effector memory CD4 T cells are responsible for the generation of clinically measurable delayed type hypersensitivity and that central memory CD4T cells are not directly involved in this process We base this idea on the assumption that latent tuberculosis is a state of antigen persistence and that effector memory T cells should be maintained as long as antigeninfection is present
We propose to conduct this study in Mali West Africa and local clinics in the US Tuberculosis affects 5931000002 individuals in Mali and most have been exposed to the disease Additionally it would be important to evaluate the same parameters locally as latent infection is one of the major factors for reactivation tuberculosis in this country Patients would be enrolled in 4 major groups HIV-TST- Group A HIV-TST Group B HIVTST Group C and HIVTST- Group D
To evaluate this hypothesis we plan to enroll between 100 - 300 patients over the course of 2 years from both countries Blood samples before and at predetermined time points after the application of Purified Protein Derivative PPD will be obtained to determine the fraction of CD4 T cells which produce interferon gamma in response to stimulation with PPD with a 16hr antigen stimulation assay Appropriate staining will be done to ascertain the phenotype as well as cytokine production Interferon gamma IFN gamma Interleukin 2 IL2 and Tumour Necrosis Factor TNF Additionally lymphocyte proliferation will be studied using 5-and-6-carboxyflouorescein diacetate succinimidyl ester CFSE
In conducting this study we hope to further the understanding of the immune mechanisms involved particularly mechanisms of T cell memory which would provide insights into TB and HIV pathogenesis We also believe that understanding these mechanisms could lead towards establishment of surrogates for immunity in TB vaccine studies which could enhance vaccine trial design It might also help in understanding better the immunological dynamics of tuberculosis co-infection in individuals with HIV infection
The purpose of the present study is to evaluate the latent form of this infection the prevalence of which worldwide exceeds that of active disease Our hypothesis is that in latent tuberculosis antigen specific effector memory CD4 T cells are responsible for the generation of clinically measurable delayed type hypersensitivity and that central memory CD4T cells are not directly involved in this process We base this idea on the assumption that latent tuberculosis is a state of antigen persistence and that effector memory T cells should be maintained as long as antigeninfection is present
We propose to conduct this study in Mali West Africa and local clinics in the US Tuberculosis affects 5931000002 individuals in Mali and most have been exposed to the disease Additionally it would be important to evaluate the same parameters locally as latent infection is one of the major factors for reactivation tuberculosis in this country Patients would be enrolled in 4 major groups HIV-TST- Group A HIV-TST Group B HIVTST Group C and HIVTST- Group D
To evaluate this hypothesis we plan to enroll between 100 - 300 patients over the course of 2 years from both countries Blood samples before and at predetermined time points after the application of Purified Protein Derivative PPD will be obtained to determine the fraction of CD4 T cells which produce interferon gamma in response to stimulation with PPD with a 16hr antigen stimulation assay Appropriate staining will be done to ascertain the phenotype as well as cytokine production Interferon gamma IFN gamma Interleukin 2 IL2 and Tumour Necrosis Factor TNF Additionally lymphocyte proliferation will be studied using 5-and-6-carboxyflouorescein diacetate succinimidyl ester CFSE
In conducting this study we hope to further the understanding of the immune mechanisms involved particularly mechanisms of T cell memory which would provide insights into TB and HIV pathogenesis We also believe that understanding these mechanisms could lead towards establishment of surrogates for immunity in TB vaccine studies which could enhance vaccine trial design It might also help in understanding better the immunological dynamics of tuberculosis co-infection in individuals with HIV infection
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-I-0030 | None | None | None |