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

Latent Tuberculosis Clinical Trial

— TB-LIVE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05621343
• Other study ID #: 2021-04885
• Status: Recruiting
• Start date: December 21, 2021
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Region Skane
• Contact: Petter Holmberg, PhD student
• Phone: +4640333108
• Email: petter.holmberg[@]med.lu.se
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Description:

Tuberculosis (TB) is the second leading cause of death due to a single infectious agent, with the main burden in resource-limited settings and in vulnerable populations. It is estimated that approximately 25% of the global population is infected with TB. LTBI is a condition where the mycobacteria rests within the body instead of creating active disease. About half of the active TB cases develop within 2 years of exposure and the other half reactivates as distant as several decades post exposure. Persistence of viable bacilli is a prerequisite for the reactivation of TB.

Through sampling of peripheral blood the investigators will investigate how selected cytokines, enzyme activity and gene expression changes during course of treatment, 4-6 months, and during follow up, 1 year. These patterns will be compared to the patterns of patients with: latent TB without treatment, active TB with treatment as well as healthy controls. Samples will be drawn at 0, 1, 6 and 12 months, after treatment initialization when applicable. Healthy controls will only be sampled once. Most of the analysis will be performed on TB-antigen stimulated blood.

The investigators hypothesize that there is a substantial fraction of latent TB patients who do not harbor live mycobacteria and that this is reflected in study outcome measures when given treatment. Furthermore, the investigators hypothesize that this fraction of latent TB patients will resemble healthy controls in terms of outcome measures whereas their counterpart, latent TB patients harboring living bacteria, will not.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 100 Years

Eligibility

LTBI (2 groups)

Inclusion Criteria:

• latent tuberculosis: Interferon gamma (IFN-?) >0.70 IU/ml in the Quantiferon-TB Plus assay

• age 15-25 years OR high likelihood of recent TB transmission

• informed consent

Exclusion Criteria:

• active tuberculosis

• chronic illness

• immunosuppressive treatment

• pregnancy (including 6 months post-partum)

• previous treatment for either active or latent TB infection

Controls

Inclusion Criteria:

• age 15-25 years

• informed consent

Exclusion Criteria:

• 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

Inclusion Criteria:

• diagnosed with active TB

• informed consent

Exclusion Criteria:

age < 15 years

Related Conditions & MeSH terms

• Latent Tuberculosis
• Mycobacterium Tuberculosis
• Persistent Infection
• Tuberculosis

Locations

Country	Name	City	State
Sweden	Skåne University Hospital	Malmö	Skåne

Sponsors (1)

Lead Sponsor	Collaborator
Region Skane

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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