CompletedNot Applicable

Evaluation of New Biomarker-based Approaches for Improving the Diagnosis of Childhood Tuberculous Meningitis

South Africa332 participantsStarted 2020-04-01

Plain-language summary

The rapid diagnosis of tuberculosis (TB) in children remains a serious challenge owing to limitations in the existing diagnostic tests. TB meningitis (TBM), an extrapulmonary form of TB, is the most severe manifestation of paediatric TB. TBM results in high morbidity and mortality in children, despite the availability of chemotherapy, mainly due to diagnostic delay. Most tests required for proper TBM diagnosis including analysis of cerebrospinal fluid (CSF) and brain imaging are not available in resource-limited settings e.g., in most of Africa including South Africa. New tests for TBM are urgently needed. The main goal of this proposal is to develop a point-of-care (POC) diagnostic test for TBM, based on CSF and bloodbiomarkers. Aim 1: Evaluate the diagnostic potentials of 51 host inflammatory biomarkers that the investigators recently identified in CSF and blood samples from children with suspected meningitis in a repository of 100 stored CSF and serum samples using a multiplex platform. After statistical analysis including multi-marker modelling by linear discriminant analysis, random forest, and other modelling techniques, the investigators will select the best combination of up to four biomarkers for incorporation into the prototype diagnostic test (Aim 2). Aim 2: Incorporate the best performing CSF and serum biomarkers into a novel, patented biosensor-based POC diagnostic test. The investigators will develop a multi-biomarker prototype test for detecting up to 4 biomarkers in serum or CSF. Aim 3: Evaluate the newly developed POC test on 300 children prospectively. This will be done at the Tygerberg Academic Hospital. The diagnostic yield of the POC test will be compared to the routine diagnostic tests.

Who can participate

Age range

3 Months – 13 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Children between the ages of 3 months and 13 years with suspected meningitis, and who require CSF examination for routine diagnostic purposes at Tygerberg Children's Hospital. * Written informed consent will be obtained from parents for inclusion of children 3 months to 7 years old in the study. * If possible, assent will be obtained in those children older than 7 years who have a normal level of consciousness, i.e. a Glasgow Coma Score (GCS) of 15/15. Exclusion Criteria: * Children 13 years and older will be excluded from the study. * Failure to obtain written consent will also exclude children from the study.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Identify CSF or blood-based biosignatures for the diagnosis of TBM in children

Timeframe: 2019-2021

Develop a prototype POC diagnostic test platform based on the biosignatures.

Timeframe: 2020-2022

Evaluate the newly developed test in a new patient cohort.

Timeframe: 2023-2024

Trial details

NCT IDNCT04308928

SponsorUniversity of Stellenbosch

Sponsor typeOTHER

Study typeOBSERVATIONAL

Primary completion2024-10-31

View on ClinicalTrials.gov More Tuberculous Meningitis trials