Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT05202548
Other study ID # 002/AMD-SP2H/LT-MULTIPDPK/LL7
Secondary ID
Status Completed
Phase
First received
Last updated
Start date May 1, 2021
Est. completion date June 25, 2021

Study information

Verified date January 2022
Source Universitas Katolik Widya Mandala Surabaya
Contact n/a
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial Summary

Mycobacterium tuberculosis (M. tuberculosis) infection is still a problem that cannot be overcome in Indonesia. In 2018 the number of tuberculosis (TB) sufferers in Indonesia reached more than 850/100,000 population, an increase around 20% from the previous year's incidence. One of the highest number of cases is in East Java Province, which is 38% of the total number of new TB cases in Indonesia. Extrapulmonary tuberculosis (EPTB) according to WHO classification criteria is an M. tuberculosis infection that occurs in tissues and organs outside the lung parenchyma. The incidence rate in Indonesia reaches 1-5% of the incidence of TB thus EPTB may often be forgotten. However, the diagnosis, therapy and monitoring post treatment in EPTB remains difficult to do. The focus of this research is tuberculous lymphadenitis (TB), due to 50% of EPTB cases in Indonesia was lymphadenitis TB. The risk factors for EPTB are immunocompromised conditions, such as HIV infection or comorbid conditions such as chronic kidney disease (CKD) and diabetes mellitus, but the mechanism of EPTB homing is still unclear. The mechanism of EPTB homing, especially TB lymphadenitis, really needs to be known for the development of diagnostics and therapy as well as preventing the occurrence of TB lymphadenitis. The importance of this research is to obtain compounds from the human immune response that can be developed as diagnostic markers and therapeutic targets for tuberculosis infection, especially TB lymphadenitis. Activated macrophages containing M. tuberculosis are carried by lymph flow to lymph nodes, where there is deposition of antigen-antibody complexes which then activate CC Chemokine Receptor-2 (CCR2) on lymphocytes, which are the primary receptors for Chemokine (CC motif) ligands ( CCL)-8 and CCL5, proteins expressed on macrophages containing M. tuberculosis. Activation of CCR2 increases the production of IL-10(10). IL-10 has been responsible for decreasing the secretion of TNF-, IFN-γ, and IL-1β (11). IFN-γ affects the process of M. tuberculosis elimination and the success of TB therapy, so that IL-10 is responsible for the failure of macrophages to eliminate M. tuberculosis. IL-10 also binds to Signal Transducer and Activator of Transcription 3 (STAT3) and STAT3 increases the release of Suppressor of Cytokine Signaling 3 (SOCS3). SOCS3 interferes with IFN-γ signaling for CCR2 recognition of M. tuberculosis-containing macrophages. On the other hand, the mechanism of T lymphocytes and macrophages that activate pro-inflammatory mediators (TNF-, IFN-γ, and IL-1β) and the association of IL-10 activation on STAT3, SOCS3 and CCR2 expression in the incidence of EPTB, especially TB lymphadenitis without TB infection remains unknown.


Description:

Mycobacterium tuberculosis (M. tuberculosis) infection is still a problem that cannot be overcome in Indonesia. In 2018 the number of tuberculosis (TB) sufferers in Indonesia reached more than 850/100,000 population, an increase around 20% from the previous year's incidence. One of the highest number of cases is in East Java Province, which is 38% of the total number of new TB cases in Indonesia. Extrapulmonary tuberculosis (EPTB) according to WHO classification criteria is an M. tuberculosis infection that occurs in tissues and organs outside the lung parenchyma. The incidence rate in Indonesia reaches 1-5% of the incidence of TB thus EPTB may often be forgotten. However, the diagnosis, therapy and monitoring post treatment in EPTB remains difficult to do. The focus of this research is tuberculous lymphadenitis (TB), due to 50% of EPTB cases in Indonesia was lymphadenitis TB. The risk factors for EPTB are immunocompromised conditions, such as HIV infection or comorbid conditions such as chronic kidney disease (CKD) and diabetes mellitus, but the mechanism of EPTB homing is still unclear. The mechanism of EPTB homing, especially TB lymphadenitis, really needs to be known for the development of diagnostics and therapy as well as preventing the occurrence of TB lymphadenitis. The importance of this research is to obtain compounds from the human immune response that can be developed as diagnostic markers and therapeutic targets for tuberculosis infection, especially TB lymphadenitis. Activated macrophages containing M. tuberculosis are carried by lymph flow to lymph nodes, where there is deposition of antigen-antibody complexes which then activate CC Chemokine Receptor-2 (CCR2) on lymphocytes, which are the primary receptors for Chemokine (CC motif) ligands ( CCL)-8 and CCL5, proteins expressed on macrophages containing M. tuberculosis. Activation of CCR2 increases the production of IL-10(10). IL-10 has been responsible for decreasing the secretion of TNF-, IFN-γ, and IL-1β (11). IFN-γ affects the process of M. tuberculosis elimination and the success of TB therapy, so that IL-10 is responsible for the failure of macrophages to eliminate M. tuberculosis. IL-10 also binds to Signal Transducer and Activator of Transcription 3 (STAT3) and STAT3 increases the release of Suppressor of Cytokine Signaling 3 (SOCS3). SOCS3 interferes with IFN-γ signaling for CCR2 recognition of M. tuberculosis-containing macrophages. On the other hand, the mechanism of T lymphocytes and macrophages that activate pro-inflammatory mediators (TNF-, IFN-γ, and IL-1β) and the association of IL-10 activation on STAT3, SOCS3 and CCR2 expression in the incidence of EPTB, especially TB lymphadenitis without TB infection remains unknown. In this study, Lymphadenitis TB paraffin blocks from patients were collected and screened for immunological responses that TB patients have potential as targets for diagnosis and therapy. The paraffin block samples came from the Anatomical Pathology Laboratory of St. Catholic Hospital. Vincentius A Paulo (RKZ) Surabaya. Existing samples were taken and performed immuno-histochemical (IHC) to define theimmune dysregulation in TB lymphadenitis.


Recruitment information / eligibility

Status Completed
Enrollment 45
Est. completion date June 25, 2021
Est. primary completion date June 25, 2021
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility Inclusion Criteria: - Lymphadenitis TB blocked paraffin that already confirmed by the Pathologist and MPT64 staining Exclusion Criteria: - broken blocked paraffin due to the storage process

Study Design


Related Conditions & MeSH terms


Intervention

Other:
Immuno-histochemical staining
blocked paraffin that suit with inclusion and exclusion criteria proceed with immuno-histochemical staining to define immune dysregulation in lymphadenitis TB

Locations

Country Name City State
Indonesia Vincentius A Paulo Surabaya Hospital Surabaya East Java

Sponsors (2)

Lead Sponsor Collaborator
Universitas Katolik Widya Mandala Surabaya Indonesia's Ministry of Research and Technology (Ristekdikti/BRIN)

Country where clinical trial is conducted

Indonesia, 

Outcome

Type Measure Description Time frame Safety issue
Primary IHC slides Histopathology slides stained by immuno-histochemical substrates 15 November 2021
See also
  Status Clinical Trial Phase
Recruiting NCT06154915 - Immune Cells in Diabetic Chronic Foot Ulcers
Completed NCT04010396 - Immunological Responses in Bovine vs Mechanical Composite Grafts
Completed NCT04586894 - Adverse Myocardial and Vascular Side Effects of Immune Checkpoint Inhibitors
Recruiting NCT04304768 - Opioid, HIV and Immune System Phase 4
Recruiting NCT05509075 - Nutraceuticals and Functional Foods
Completed NCT02140216 - Immunomodulation Effect of Blood Transfusion
Completed NCT03793309 - Different Doses of Vitamin D and T Regulatory Cells in Preterm Infants Phase 1
Recruiting NCT05867004 - Blocking TNF to Potentiate the ICI-dependent Immune Awakening in Melanoma
Completed NCT02460328 - Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome N/A