Mycobacterium Tuberculosis, Tuberculosis, Extra-Pulmonary, Tuberculosis, Pulmonary
Conditions
Keywords
cfDNA
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
Interventions
None listed
Sponsors
University of Oxford
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| 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) |
Countries
Thailand
Contacts
CONTACTHtet Ko Ko Aung, Dr
CONTACTFrançois Nosten, Professor
PRINCIPAL_INVESTIGATORTimothy Seers, Dr
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University.
Outcome results
None listed