Clinical trial NCT06580639: The Role of a Mycobacterium Growth Inhibition Assay to Quantify Host Immune Control of M. Tuberculosis
Official title: 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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Tuberculosis
Immunologic Activity Alteration
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
First posted: 2024-08-30
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects who are attending the infectious disease clinics at region Östergötland och region Kalmar, Sweden.

Brief summary: 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: 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.

Eligibility 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.

Primary outcomes:
measure: Mycobacterial inhibition of host macrophages
timeFrame: Up to 10 days incubation
measure: Mycobacterial inhibition of host peripheral blood mononuclear cells (PBMCs)
timeFrame: Up to 10 days incubation
Secondary outcomes:
measure: Cytokine expression of host peripheral blood mononuclear cells (PBMCs)
timeFrame: 24 hours
Other outcomes:
Locations:
city: Kalmar
country: Sweden
facility: Kalmar County Hospital
city: Linköping
country: Sweden
facility: Dept of Infectious Diseases
Study officials:
affiliation: Linkoeping University
name: Thomas Schoen, Professor
role: PRINCIPAL_INVESTIGATOR
References: