Blood Tuberculosis DNA Levels to Monitor Tuberculosis Treatment

Not yet recruiting

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

• Registration Number: NCT06845618
• Lead Sponsor: University of Oxford

Brief Summary

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

Detailed Description

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

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-19
• Study First Submitted QC: 2025-02-19
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-03-27
• Study Start: 2025-05-01
• Primary Completion: 2027-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 140

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Mtb-cfDNA trajectories	Day 0 - 168 (or end of treatment)	Rate of Mtb-cfDNA clearance derived from serial Mtb-cfDNA measurements
Percentage of participants completing sampling schedule	Day 0 - 168 (or end of treatment)

Secondary Outcome Measures

Name	Time	Method
Exploratory analysis is planned and will compare Mtb-cfDNA levels to clinical, microbiological and radiological features	Day 0 - 168 (or end of treatment)

Trial Locations

Locations (1)

Shoklo Malaria Research Unit (SMRU); 🇹🇭 Tak, Thailand