Clinical trial NCT06845618: Blood Tuberculosis DNA Levels to Monitor Tuberculosis Treatment
Official title: Mycobacterium Tuberculosis Complex Cell-free DNA (Mtb-cfDNA) for the Pharmacometric Assessment of Anti-tuberculosis Treatment: a Proof-of-concept Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Mycobacterium Tuberculosis
Tuberculosis, Pulmonary
Tuberculosis, Extra-Pulmonary
Keywords: cfDNA
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2025-02-25
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Mtb-cfDNA trajectories
timeFrame: Day 0 - 168 (or end of treatment)
measure: Percentage of participants completing sampling schedule
timeFrame: Day 0 - 168 (or end of treatment)
Secondary outcomes:
measure: Exploratory analysis is planned and will compare Mtb-cfDNA levels to clinical, microbiological and radiological features
timeFrame: Day 0 - 168 (or end of treatment)
Other outcomes:
Locations:
city: Tak
country: Thailand
facility: Shoklo Malaria Research Unit (SMRU)
Study officials:
affiliation: Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University.
name: Timothy Seers, Dr
role: PRINCIPAL_INVESTIGATOR
References: