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

August 28, 2024 updated by: Thomas Schon, Linkoeping University

The Role of a Mycobacterium Growth Inhibition Assay to Quantify Host Immune Control of M. Tuberculosis From Healthy Blood Donors and Patients With Latent or Active Tuberculosis.

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?

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

280

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Sweden
      • Kalmar, Sweden, 391 85
        • Recruiting
        • Kalmar County Hospital
        • Contact:
      • Linköping, Sweden, 581 85
        • Recruiting
        • Dept of Infectious Diseases
        • Contact:
        • Sub-Investigator:
          • Jakob Paues, MD PhD
        • Sub-Investigator:
          • Katarina Niward, MD PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Subjects who are attending the infectious disease clinics at region Östergötland och region Kalmar, Sweden.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Healthy Individuals
Patients with a negative IGRA (Quantiferon) who are apparently healthy.
Other: No intervention.
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.
Other: No intervention.
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.
Other: No intervention.
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.
Other: No intervention.
Blood sampling for analysis of mycobacterial growth inhibition assay (MGIA) analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mycobacterial inhibition of host macrophages
Time Frame: Up to 10 days incubation
Mycobacterial inhibition of host macrophages
Up to 10 days incubation
Mycobacterial inhibition of host peripheral blood mononuclear cells (PBMCs)
Time Frame: Up to 10 days incubation
Mycobacterial inhibition of host peripheral blood mononuclear cells (PBMCs)
Up to 10 days incubation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cytokine expression of host peripheral blood mononuclear cells (PBMCs)
Time Frame: 24 hours
Proteome analysis following exposure of PBMCs to gamma-irradiated M. tuberculosis
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Linkoeping University

Investigators

  • Principal Investigator: Thomas Schoen, Professor, Linkoeping University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2020

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

August 28, 2024

First Submitted That Met QC Criteria

August 28, 2024

First Posted (Actual)

August 30, 2024

Study Record Updates

Last Update Posted (Actual)

August 30, 2024

Last Update Submitted That Met QC Criteria

August 28, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-06858-02

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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