Blood Tuberculosis DNA Levels to Monitor Tuberculosis Treatment (Mtb-Dynamic)

University of Oxford

Status: Not yet enrolling

Conditions: Tuberculosis, Extra-Pulmonary; Tuberculosis, Pulmonary; Mycobacterium Tuberculosis

Study type: Observational

Funder types: Other

Identifiers

NCT06845618

MYC24003

Details and patient eligibility

About

Tuberculosis (TB) is a leading infectious cause of death worldwide. Current strategies for monitoring TB treatment response are culture dependent and insensitive. New methods of assessing treatment response in vivo could inform new drug development and other treatment strategies. Cell-free DNA (cfDNA) - small circulating fragments of DNA - is widely used in maternofetal medicine and oncology for diagnosis and assessment of treatment response. This study aims to investigate whether pathogen derived Mycobacterium tuberculosis-specific cfDNA (Mtb-cfDNA) can be used to monitor TB treatment response.

This feasibility study will take place at Mae RaMat TB Center in Thailand and includes two study groups:

1. Assay Development and Validation
2. Longitudinal Assessment of Mtb-cfDNA levels

Full description

This study is funded by the Wellcome Trust; grant reference number: 223099/Z/21/Z

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Participants with a new diagnosis of tuberculosis

• Aged ≥ 18 years old
• Newly microbiologically confirmed (culture or nucleic acid amplification test) diagnosis of Mycobacterium tuberculosis (Mtb.) infection (of any site)
• Has not yet commenced antituberculosis therapy
• Able to understand study procedures and requirements and is able to give informed consent

For healthy volunteers:

• Aged ≥ 18 years old
• Healthy as judged by a responsible physician
• Able to understand study procedures and requirements and is able to give informed consent

Exclusion criteria

Participants with a new diagnosis of tuberculosis

• Exposure to antituberculosis treatment in the last 8 weeks (or Mycobacterium tuberculosis (Mtb.) active fluoroquinolone)
• Known history of underlying malignancy
• Pregnancy
• Transfusion dependent anaemia

For healthy volunteers:

• History of tuberculosis infection or latent tuberculosis infection
• Household, or other close contact, of a person living with tuberculosis disease
• Chest radiograph (CXR) changes suggestive of pulmonary tuberculosis
• Presence of symptoms which would otherwise indicate screening for tuberculosis (cough > 2 weeks duration, fever, weight loss, night sweats)
• Other major medical comorbidity
• Pregnancy
• Known malignancy

Trial design

140 participants in 2 patient groups

Group 1: Assay development and validation

Description:

Twenty participants with a new diagnosis of tuberculosis will have venous blood collected prior to treatment initiation. Twenty participants without clinical evidence of tuberculosis infection will be recruited from the local community as a control during assay validation. This group of the study participants will be assessed at day zero only.

Group 2: Longitudinal Assessment

Description:

In this group, tuberculosis participants (n= 120) will have longitudinal sampling performed from diagnosis to the end of treatment. This will establish the feasibility of dynamic Mtb-cfDNA measurements for the assessment of tuberculosis treatment response.