The Role of a Mycobacterium Growth Inhibition Assay to Quantify Host Immune Control of M. Tuberculosis

NCT ID: NCT06580639

Last Updated: 2024-08-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

280 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-08-01

Study Completion Date

2025-12-01

Brief Summary

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The goal of this observational study is to learn about how the blood leucocytes from patients with and without exposure or disease from tuberculosis (TB) are able to kill live mycobacteria (M. tuberculosis). The main question it aims to answer is:

Is intracellular growth suppression of M. tuberculosis in peripheral blood mononuclear cells variable among healthy blood donors and higher than in patients with latent TB compared to active TB?

Detailed Description

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Background: The host immune response is crucial in determining the outcome after exposure to Mtb. A substantial proportion of exposed individuals (40-70%) never develop infection indicating an efficient cell mediated immune response against Mtb and early clearance by the host immune defense (Verall et al, Immunology 2014). Thus, the outcome of exposure is highly dependent on host immunity. In this study, our aim was to investigate whether the previously developed mycobacterium groth inhibition assay (MGIA) method (Andersson et al, Tuberculosis 2020) could be used to quantify the host immune response to Mtb.

Study design: In this study we will include healthy donors (n=80), patient with active TB (n=40), subjects recently exposed to active TB (n=80) and patients with latent TB (LTBI) (n=80). Exclusion criteria for all groups are known HIV infection or other immunosuppression from treatment or disease. Patients and healthy blood donors will be recruited at the departments of infectious diseases in Region Kalmar and Region Östergötland. From patients giving oral and written consent, 40 ml of blood will be collected for MGIA analysis.

Primary aim: To determine the difference in MGIA between healthy blood donors and patients with latent and active TB as well as the variation in host control of Mtb within each group.

Method: The Mycobacterial growth inhibition assay (MGIA) using human PBMCs isolated by density gradient by Lymhoprep (Axis-Shield) and SepMate tubes (StemCell Technologies) will be performed as described in study I with minor modifications. The PBMCs are infected with GFP expressing M. tuberculosis H37Rv and intracellular growth of Mtb and viability of PBMCs are assessed by live-cell imaging (Incucyte©) and measured as relative fluorescence units (RFU) during 5 days with and without stimulation with the purified protein derivate (PPD) is included. The cytokine response following exposure to gamma-irradiated H37Rv will be quantified by Olink proteomics.

Conditions

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Tuberculosis Immunologic Activity Alteration

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Healthy Individuals

Patients with a negative IGRA (Quantiferon) who are apparently healthy.

No intervention.

Intervention Type OTHER

Blood sampling for analysis of mycobacterial growth inhibition assay (MGIA) analysis.

Close contacts to patients with active TB

Close contacts to patients with active, smear positive pulmonary TB.

No intervention.

Intervention Type OTHER

Blood sampling for analysis of mycobacterial growth inhibition assay (MGIA) analysis.

Patients with (latent) tuberculosis infection

Patients without active TB who have a positive IGRA (Quantiferon Plus) result.

No intervention.

Intervention Type OTHER

Blood sampling for analysis of mycobacterial growth inhibition assay (MGIA) analysis.

Patients with active TB

Culture or PCR-verified active TB who are initiated on treatment.

No intervention.

Intervention Type OTHER

Blood sampling for analysis of mycobacterial growth inhibition assay (MGIA) analysis.

Interventions

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No intervention.

Blood sampling for analysis of mycobacterial growth inhibition assay (MGIA) analysis.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

Inclusion Criteria: Healthy blood donors or subjects who will get vaccinated.

Exclusion Criteria:Known HIV infection, not Swedish citizen, chronic liver och kidney disease,immunosuppression from treatment or disease.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Linkoeping University

OTHER_GOV

Sponsor Role lead

Responsible Party

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Thomas Schon

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thomas Schoen, Professor

Role: PRINCIPAL_INVESTIGATOR

Linkoeping University

Locations

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Kalmar County Hospital

Kalmar, , Sweden

Site Status RECRUITING

Dept of Infectious Diseases

Linköping, , Sweden

Site Status RECRUITING

Countries

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Sweden

Central Contacts

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Thomas Schoen, Professor

Role: CONTACT

Phone: +48013580000

Email: [email protected]

Facility Contacts

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Thomas Schön, Professor

Role: primary

Thomas Schön, Professor

Role: primary

Other Identifiers

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2022-06858-02

Identifier Type: -

Identifier Source: org_study_id