New Strategies for Assessment of the Persistence of Viable Bacilli in Latent and Active Tuberculosis

NCT05621343 | Recruiting

• 1 other identifier: 2021-04885
• Study Type: observational
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

Current diagnostic tools such as interferon gamma release assay (IGRA) and purified protein derivative (PPD) can not distinguish patients with latent tuberculosis infection (LTBI) and persistence of live mycobacteria. This inability to rule out living mycobacteria in patients investigated for LTBI leads to unnecessary and potentially harmful treatment regimes all around the globe. The goal of this observational study is to identify candidate biomarkers for viable bacilli in latent tuberculosis in order to decrease the use of unnecessary and ineffective antibiotic treatment.

Conditions

Latent Tuberculosis; Persistent Infection; Mycobacterium Tuberculosis

Outcome Measures

Primary Outcomes (3)

• Cytokine levels

  To determine levels of selected cytokines in supernatants of Mtb-incubated whole blood obtained from persons diagnosed with LTBI during the course of treatment, and to identify patterns of cytokine expression suggestive of bacterial eradication.

  0-12 months

• Gene expression

  To characterize patterns of small non-coding RNA (sncRNA) expression (including microRNAs) in blood and plasma from persons diagnosed with LTBI, and to identify patterns of sncRNA expression in individuals with LTBI suggestive of bacterial eradication.

  0-12 months

• Activity of indoleamine 2, 3-dioxygenase (IDO)

  3\. To characterize IDO activity in plasma from persons diagnosed with LTBI, and to determine whether changes in IDO activity during the course of LTBI reflect bacterial eradication

  0-12 months

Study Arms (4)

Latent TB on treatment

Treatment according to existing Swedish guidelines with: Oral rifampicin 10 mg/kg (max 600mg) once daily during 4 months OR Oral isoniazide 5 mg/kg (max 300mg) once daily in combination with 40mg vitamin B6 (pyridoxin) during 6 months

Latent TB not on treatment

Latent TB without indication for treatment OR patient who do not want to receive treatment

Active TB with treatment

Treatment according to existing Swedish guidelines. Duration and choice of antibiotic therapy depending on the condition.

Healthy control

Healthy

Eligibility Criteria

• Age: 15 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals 15 years or older diagnosed with latent- or active tuberculosis or found healthy as part of routine care at the out- and inpatient department of the department for infectious diseases at Skåne University Hospital in Malmö, Sweden

You may qualify if:

• latent tuberculosis: Interferon gamma (IFN-γ) \>0.70 IU/ml in the Quantiferon-TB Plus assay
• age 15-25 years OR high likelihood of recent TB transmission
• informed consent

You may not qualify if:

• active tuberculosis
• chronic illness
• immunosuppressive treatment
• pregnancy (including 6 months post-partum)
• previous treatment for either active or latent TB infection
• Controls
• age 15-25 years
• informed consent
• latent- OR active tuberculosis
• chronic illness
• immunosuppressive treatment
• pregnancy (including 6 months post-partum)
• previous treatment for either active or latent TB infection
• Active TB
• diagnosed with active TB

Sponsors & Collaborators

• Region Skane: lead

Study Sites (1)

Skåne University Hospital

Malmo, Skåne County, 20502, Sweden

RECRUITING

Related Publications (1)

• Holmberg P, Janouskova M, Schmidt T, Neumann A, Olsson O, Isberg PE, Reimann M, Riesbeck K, Skogmar S, Bjorkman P. Blood levels of Mycobacterium tuberculosis (Mtb)antigen-triggered immune markers in people exposed to tuberculosis with regard to Mtb infection status and receipt of tuberculosis preventive therapy. Tuberculosis (Edinb). 2025 Mar;151:102595. doi: 10.1016/j.tube.2024.102595. Epub 2024 Dec 20.

  PMID: 39742565 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood

MeSH Terms

Conditions

Latent Tuberculosis; Persistent Infection

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Per Björkman, Professor

  Lund University, Faculty of Medicine, Department of Translational Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Petter Holmberg, PhD student

CONTACT

+4640333108; petter.holmberg@med.lu.se

Per Björkman, Professor

CONTACT

per.bjorkman@med.lu.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: November 18, 2022
• Study Start: December 21, 2021
• Primary Completion: June 1, 2024
• Study Completion: December 1, 2024
• Last Updated: June 18, 2024

Record last verified: 2024-04

Locations

SE (1)