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

Mycobacterium Tuberculosis Complex Cell-free DNA (Mtb-cfDNA) for the Pharmacometric Assessment of Anti-tuberculosis Treatment: a Proof-of-concept Study

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

Study Overview

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

Detailed Description

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

• Study Type: Observational
• Enrollment (Estimated): 140

Contacts and Locations

• Study Contact: Name: Htet Ko Ko Aung, Dr; Phone Number: 109 055 581 135; Email: htetkoko@shoklo-unit.com
• Study Contact Backup: Name: François Nosten, Professor; Phone Number: 055 532026; Email: francois@tropmedres.ac

Study Locations

• Thailand
  • Tak, Thailand
    • Recruiting
    • Shoklo Malaria Research Unit (SMRU)
    • Contact: Htet Ko Ko Aung, Dr; Phone Number: 109 055 581 135; Email: htetkoko@shoklo-unit.com
    • Contact: François Nosten, Professor; Phone Number: 055 532026; Email: francois@tropmedres.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Group 1: Assay development and validation. In this group, sampling will be performed at tuberculosis diagnosis. Tuberculosis participants (n = 20) will have blood sampling performed at day 0. Healthy participants (n = 20) without clinical evidence of tuberculosis will have blood sampling performed at a single timepoint.

Group 2: Longitudinal Assessment. In this group, tuberculosis participants (n= 120) will have longitudinal sampling performed from diagnosis to the end of treatment. This will help to establish the feasibility of dynamic Mtb-cfDNA measurements.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Group 1: Assay development and validation; 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; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Oxford
• Investigators: Principal Investigator: Timothy Seers, Dr, Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: February 19, 2025
• First Submitted That Met QC Criteria: February 19, 2025
• First Posted (Actual): February 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: cfDNA
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Extrapulmonary; Tuberculosis, Pulmonary
• Other Study ID Numbers: MYC24003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data generated in this study belongs to the study group as a whole. The final database will be shared amongst the PI and key members of the research team.

With participant's consent, clinical data and results from blood analyses stored in the database may be shared with researchers not directly involved in this study but only after the main paper has been published and in accordance with MORU guidelines on data sharing.

The results of the study will be summarised in lay language, in both English and the language(s) commonly spoken at the study site, and disseminated to participants and the community.

The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. Authorship will be determined in accordance with the International Committee of Medical Journal Editors (ICMJE) guidelines and other contributors will be acknowledged.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No