Blood Tuberculosis DNA Levels to Monitor Tuberculosis Treatment

NCT06845618 | Recruiting

• 1 other identifier: MYC24003
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

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

Conditions

Mycobacterium Tuberculosis; Tuberculosis, Pulmonary; Tuberculosis, Extra-Pulmonary

Keywords

cfDNA

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Exploratory analysis is planned and will compare Mtb-cfDNA levels to clinical, microbiological and radiological features

  Day 0 - 168 (or end of treatment)

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Shoklo Malaria Research Unit (SMRU)

Tak, Thailand

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Biological specimens will be collected, processed, stored and shipped in concordance with established standard operating procedures. Blood will be collected following best practice venepuncture technique. Blood samples will be transferred by vehicle to the main SMRU laboratory in a cool box within six hours. The leftover blood samples will be stored and may be used for future studies for up to 30 years. Anonymised samples may be shared with collaborators internationally for further analysis. Consent will be obtained from participants for sample storage and future use of specimen. Any proposed plans to use samples other than for those investigations detailed in this protocol will be submitted to the relevant ethics committees prior to any testing.

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis, Extrapulmonary

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Timothy Seers, Dr

  Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Htet Ko Ko Aung, Dr

CONTACT

055 581 135; htetkoko@shoklo-unit.com

François Nosten, Professor

CONTACT

055 532026; francois@tropmedres.ac

Study Design

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

Study Record Dates

• First Submitted: February 19, 2025
• First Posted: February 25, 2025
• Study Start: July 21, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

TH (1)