Quantitative Measurement of Plasma and Urine MTB Cell-free DNA Level
LIQUID-TB
1 other identifier
observational
85
1 country
2
Brief Summary
Tuberculosis (TB) is one of the leading causes of infectious disease worldwide. The diagnosis of TB typically relies on microbiological evidence of the presence of Mycobacterium tuberculosis (MTB) or histological features of the host immune response to MTB in the infected organs. The diagnosis can be enhanced by performing molecular diagnostic tests (e.g. polymerase chain reaction, PCR) on the clinical specimens obtained. Expectorated sputum is usually the first sample sent for MTB culture for suspected pulmonary TB (PTB), which is the most common type of TB. However, this can be particularly challenging for paediatric patients and elderly patients with poor coughing techniques or effort. While for extrapulmonary TB (EPTB), which contributes to 10-20% of TB cases, with TB pleuritis and lymphadenitis as the most common types, invasive investigations are usually required for obtaining clinical specimens of good quality for MTB culture or histological examination. The invasiveness of procedures (e.g. pleural biopsy, lymph node biopsy) and inadequate sensitivity of diagnostic tests could hinder the diagnosis of EPTB. The long turnaround time of MTB culture also creates a challenge for timely diagnosis. Blood sampling for MTB culture or PCR, although non-invasive, has low diagnostic yields. All these urges for non-invasive, rapid and accurate diagnosis of TB. The standard duration of TB treatment is 6 months, with a longer duration up to 12 months required for certain types of EPTB or in patients with underlying comorbidities (e.g. diabetes mellitus). Treatment monitoring and surveillance for relapses are typically based on a composite of clinical symptoms, sputum MTB culture status, and radiographical appearance. All these domains have their drawbacks, including subjective reporting (clinical symptoms), long turnaround times (sputum MTB culture status), and a lack of diagnostic sensitivity (changes in radiographical appearance in PTB). These clinical unmet needs may be overcome if a non-invasive molecular test could accurately quantify the burden of MTB in the body. Recently, it was reported that the level of MTB cfDNA in plasma can be measured by the CRISPR-TB assay. However, the data were derived mainly from the paediatric patient group and did not evaluate the possibility of latent TB infection (LTBI). This new technology remains explorative at the moment. Our group has developed a metagenomic sequencing-based assay for measuring the level of MTB cell-free DNA (cfDNA) in plasma. We hypothesize that this new plasma MTB cfDNA assay has the potential to diagnose active TB disease, treatment monitoring and surveillance monitoring by serially measuring the MTB cfDNA level in the plasma. Similar technology may also be applicable to urine, which requires prospective validation.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Feb 2026
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 5, 2025
CompletedFirst Posted
Study publicly available on registry
September 12, 2025
CompletedStudy Start
First participant enrolled
February 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2027
April 24, 2026
April 1, 2026
1.2 years
September 5, 2025
April 21, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
diagnostic performance of the plasma MTB cfDNA assay
The diagnostic performance of the plasma MTB cfDNA assay in patients with newly diagnosed TB disease
1 month
Secondary Outcomes (5)
Level of plasma MTB cfDNA level during treatment
6 months
Level of plasma MTB cfDNA level after treatment
3 months
Diagnostic performance of the urine MTB cfDNA assay
1 month
Level of urine MTB cfDNA level during treatment
6 months
Level of urine MTB cfDNA level after treatment
3 months
Study Arms (3)
TB group
patients with active TB disease
LTBI group
patients with latent TB infection
control group
subjects without active TB disease or latent TB infection
Interventions
Quantitative measurement of MTB cfDNA level in the plasma
Quantitative measurement of MTB cfDNA level in the urine
Eligibility Criteria
Patients with active TB disease will be recruited as positive control. Patients with latent TB infection, and subjects without active TB disease and latent TB infection will be recruited as negative control.
You may qualify if:
- TB group: patients hospitalized for newly diagnosed TB disease.
- LTBI group: patients without TB disease, but with LTBI diagnosed by either tuberculin skin test (TST) or an interferon-gamma release assay (IGRA) blood test.
- Control group: patients or healthy volunteers without TB disease and LTBI
You may not qualify if:
- Initiation of an effective anti-TB treatment regimen more than 24 hours
- Aged 17 years or younger
- Life expectancy of less than 12 months
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Prince of Wales Hospital
Hong Kong, Hong Kong, Hong Kong
Prince of Wales Hospital
Hong Kong, Hong Kong
Biospecimen
Blood
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Target Duration
- 12 Months
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
September 5, 2025
First Posted
September 12, 2025
Study Start
February 1, 2026
Primary Completion (Estimated)
April 30, 2027
Study Completion (Estimated)
July 31, 2027
Last Updated
April 24, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share