Ignite Creation Date:
2025-12-25 @ 12:19 AM
Ignite Modification Date:
2025-12-25 @ 10:22 PM
Study NCT ID:
NCT02225158
Status:
TERMINATED
Last Update Posted:
2017-07-02
First Post:
2014-08-23
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Immune Responses to Mycobacterium Tuberculosis (Mtb) in People With Latent Tuberculosis Infection With or Without Concomitant Helminth Infection
Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Organization:
Study Overview
Official Title:
Longitudinal Study of Immune Responses to Mycobacterium Tuberculosis (Mtb) in Subjects With Latent Tuberculosis (TB) Infection(LTBI) With or Without Concomitant Helminth Infection
Status:
TERMINATED
Status Verified Date:
2017-05-11
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:
Background:
Tuberculosis (TB) is a severe disease and a major cause of death in many people worldwide. It is caused by a bacteria that enters through the lungs and can spread elsewhere in the body. People with latent TB have the bacteria that lie dormant but can become active and cause disease. These people are offered treatment to prevent development of active TB. Worldwide, a lot of people with LTBI also have a parasitic worm called a helminth that can stay in the gut or the blood. These parasites can affect the immune system and cause diseases like TB to become worse. Researchers want to see how helminth infection makes it harder for people to fight TB infection.
Objectives:
\- To study how the immune system of people with latent tuberculosis infection (LTBI) acts to prevent development of active TB. Also, to study how helminth infection might affect this immune response.
Eligibility:
* Adults age 18 70 with LTBI as defined by an approved blood test called QuantiFERON TB Gold.
* No evidence of infections like Hepatitis or HIV
* Pregnant subjects and subjects taking medications that suppress the immune system are not eligible.
* Have not received prior treatment for LTBI. Participants might be still eligible if prior treatment for active TB has been received
Design:
Screening phase:
\- Participants will be screened with medical history, physical exam, and blood tests for other infections/conditions which might affect the immune system. They will have testing for active TB i.e. blood testing as well as testing of their spit, scans and X-rays.
Baseline phase:
* Only eligible participants will be entered into the study.
* Participants will have interviews, medical history, and physical exam.
* Blood will be drawn from an arm vein for testing.
* Participants will collect stool samples at home for 3 days in a row to test for helminth infection..
* Participants may have apheresis. Blood cells are removed by needle. They pass through a separator machine which returns everything but the cells back to the participant.
* Participants may have procedures at the start and end of the study that let researchers look into the lungs and collect cells.
Study phase, about 2 years:
* All participants will be offered treatment for LTBI which lasts 6-9 months.
* Participants being treated for LTBI will have about 11 study visits. They will visit monthly for 9 months while on treatment, then 6 and 12 months after treatment.
* Participants not eligible/refusing treatment for LTBI will be made aware of active TB, then have 3 other visits, about 6, 12, and 24 months after the baseline visit.
* Participants who have helminth infection will receive appropriate treatment.
* All participants will have blood drawn at each visit.
Tuberculosis (TB) is a severe disease and a major cause of death in many people worldwide. It is caused by a bacteria that enters through the lungs and can spread elsewhere in the body. People with latent TB have the bacteria that lie dormant but can become active and cause disease. These people are offered treatment to prevent development of active TB. Worldwide, a lot of people with LTBI also have a parasitic worm called a helminth that can stay in the gut or the blood. These parasites can affect the immune system and cause diseases like TB to become worse. Researchers want to see how helminth infection makes it harder for people to fight TB infection.
Objectives:
\- To study how the immune system of people with latent tuberculosis infection (LTBI) acts to prevent development of active TB. Also, to study how helminth infection might affect this immune response.
Eligibility:
* Adults age 18 70 with LTBI as defined by an approved blood test called QuantiFERON TB Gold.
* No evidence of infections like Hepatitis or HIV
* Pregnant subjects and subjects taking medications that suppress the immune system are not eligible.
* Have not received prior treatment for LTBI. Participants might be still eligible if prior treatment for active TB has been received
Design:
Screening phase:
\- Participants will be screened with medical history, physical exam, and blood tests for other infections/conditions which might affect the immune system. They will have testing for active TB i.e. blood testing as well as testing of their spit, scans and X-rays.
Baseline phase:
* Only eligible participants will be entered into the study.
* Participants will have interviews, medical history, and physical exam.
* Blood will be drawn from an arm vein for testing.
* Participants will collect stool samples at home for 3 days in a row to test for helminth infection..
* Participants may have apheresis. Blood cells are removed by needle. They pass through a separator machine which returns everything but the cells back to the participant.
* Participants may have procedures at the start and end of the study that let researchers look into the lungs and collect cells.
Study phase, about 2 years:
* All participants will be offered treatment for LTBI which lasts 6-9 months.
* Participants being treated for LTBI will have about 11 study visits. They will visit monthly for 9 months while on treatment, then 6 and 12 months after treatment.
* Participants not eligible/refusing treatment for LTBI will be made aware of active TB, then have 3 other visits, about 6, 12, and 24 months after the baseline visit.
* Participants who have helminth infection will receive appropriate treatment.
* All participants will have blood drawn at each visit.
Detailed Description:
Mycobacterium tuberculosis (Mtb) infection remains an important cause of morbidity and mortality worldwide. A problem for eradication efforts is the large reservoir of \~2 billion people with latent tuberculosis (TB) infection (LTBI) and poor understanding of factors leading to active disease progression. Helminth infections geographically overlap with Mtb and induce significant immune-mediated modulation. Although CD4+T cells producing IFN-gamma and TNF-alpha have been implicated in protective immunity to TB, a detailed description of the evolution of protective and immunomodulatory responses in LTBI is lacking. Additionally, there is incomplete understanding of how the immunomodulation caused by helminth co-infection affects such responses.
This protocol will attempt to fill this knowledge gap through comprehensive longitudinal immunological analyses of two populations of subjects with LTBI, with or without concurrent helminth infection (HEL+ and HEL- respectively). In both groups, venipuncture and possibly apheresis will be performed to understand protective and modulatory T cell and monocyte/macrophage responses. Subjects will receive treatment for helminth infection and treatment for LTBI will be offered according to current standard of care guidelines. Two groups of subjects within the LTBI group will be offered bronchoscopy and lavage --- (a) those with structural lung damage from prior treated/healed tuberculosis and (b) those with recent prolonged exposure (greater than or equal to 3 months) to a household contact with active TB.
The primary objective is to evaluate CD4+ T cell responses and regulatory T cell responses in HEL+ and HEL- subjects with LTBI at the time of diagnosis (baseline). HEL+ subjects will then receive treatment for parasitic infection and both groups (HEL+ and HEL-) will be offered LTBI treatment. Evolution of the baseline TB-specific immune responses on and after LTBI treatment will then be studied. Additionally, baseline immune responses to mycobacteria will be contrasted in the HEL+ group with all time points post treatment for helminth infection. A secondary objective is to evaluate the immune phenotype and functionality of tissue resident immune cells obtained by bronchoalveolar lavage in subjects with LTBI and structural lung damage from prior treated/healed pulmonary tuberculosis as well as subjects with recent prolonged TB exposure from an active TB case irrespective of helminth infection status.
An exploratory objective is to evaluate if there are subsets of subjects within the LTBI group (irrespective of helminth infection status) who have stable pool of long lasting antigen-specific IL-2 only producing CD4+ central memory T cells and changes to this pool after receiving LTBI treatment.
This protocol will attempt to fill this knowledge gap through comprehensive longitudinal immunological analyses of two populations of subjects with LTBI, with or without concurrent helminth infection (HEL+ and HEL- respectively). In both groups, venipuncture and possibly apheresis will be performed to understand protective and modulatory T cell and monocyte/macrophage responses. Subjects will receive treatment for helminth infection and treatment for LTBI will be offered according to current standard of care guidelines. Two groups of subjects within the LTBI group will be offered bronchoscopy and lavage --- (a) those with structural lung damage from prior treated/healed tuberculosis and (b) those with recent prolonged exposure (greater than or equal to 3 months) to a household contact with active TB.
The primary objective is to evaluate CD4+ T cell responses and regulatory T cell responses in HEL+ and HEL- subjects with LTBI at the time of diagnosis (baseline). HEL+ subjects will then receive treatment for parasitic infection and both groups (HEL+ and HEL-) will be offered LTBI treatment. Evolution of the baseline TB-specific immune responses on and after LTBI treatment will then be studied. Additionally, baseline immune responses to mycobacteria will be contrasted in the HEL+ group with all time points post treatment for helminth infection. A secondary objective is to evaluate the immune phenotype and functionality of tissue resident immune cells obtained by bronchoalveolar lavage in subjects with LTBI and structural lung damage from prior treated/healed pulmonary tuberculosis as well as subjects with recent prolonged TB exposure from an active TB case irrespective of helminth infection status.
An exploratory objective is to evaluate if there are subsets of subjects within the LTBI group (irrespective of helminth infection status) who have stable pool of long lasting antigen-specific IL-2 only producing CD4+ central memory T cells and changes to this pool after receiving LTBI treatment.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 14-I-0178 | None | None | View |