Host Blood RNA Signatures for Diagnosis of TB

NCT05542511 | Active Not Recruiting DMC

• 2 other identifiers: M22/02/004_Sub StudyM20/06/017TMA2020CDF-3209
• Study Type: observational
• Target: 1,458
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculosis (TB) is the biggest infectious cause of death worldwide, and the biggest cause of death in Sub-Saharan Africa among HIV-positive patients. There is need for a non-sputum-based rapid triage test that identifies individuals with presumptive TB requiring confirmatory diagnostic investigation. Such a test could reduce the burden on health systems, expedite referral and confirmatory testing, and treatment thereby reducing transmission. A non-sputum triage test is needed as many symptomatic patients including those with HIV, can often not produce high quality sputum (which most current diagnostics rely on). Several blood transcriptional diagnostic signatures produced due to immune responses to M. tuberculosis infection have previously been described, however there is lack of real-world performance data especially in high TB/HIV-endemic African settings where rates of HIV (that could compromise sensitivity) and previous TB (that could compromise specificity) are high. Furthermore, by building on prior research that used untargeted sequencing approaches to identify candidate signatures, the investigators are now at a stage to perform the targeted signature measurement at a large scale and cost-efficient manner as part of prospective diagnostic accuracy analyses in real-world settings. Using the framework provided by ongoing funded diagnostic clinical trials with similar eligibility criteria, in presumptive TB participants (≥18 years) who visit selected health facilities in Cape Town, South Africa, RADIANT has a unique opportunity to pursue several important research questions. RADIANT aims are to 1) evaluate the sensitivity and specificity of selected concise peripheral host transcriptional signatures for active TB among symptomatic persons in South Africa; 2) design a cost-optimised diagnostic algorithm based on transcriptional signatures, SeroSelectTB (an EDCTP funded pan-African evaluation of a point-of-care serological triage test for active TB) results, and confirmatory bacteriological testing, and 3) characterise bacteriologically-negative patients classified as non-TB to determine if those with elevated host transcriptional signatures have other respiratory pathogens (detected in nasopharyngeal swabs using a commercial multiplex panel) and/or develop active TB within six months (incident active TB).

Conditions

Tuberculosis; Lower Respiratory Infection

Keywords

Diagnostics; Triage; Transcriptional profiling

Outcome Measures

Primary Outcomes (1)

• Validate concise host transcriptional signatures for active TB

  Diagnostic performance of pre-described blood transcriptional signatures is measured using a cost-efficient RNA profiling method.

  24 months

Secondary Outcomes (2)

• Characterization of respiratory microorganisms

  24 months

• Detection of Incident active TB

  3 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults 18 years of age and older who self-report at the selected healthcare facilities in Cape Town, South Africa, seeking medical attention due to symptoms suggestive of tuberculosis within the parent SeroSelectTB study and consent to RADIANT.

You may qualify if:

• Adults aged 18 years and above
• Signed written informed consent or witnessed oral consent in case of illiteracy, before undertaking any study-related activities
• Are unwell and are suspected to have tuberculosis

You may not qualify if:

• Currently receiving TB treatment
• In the past 3 months, participants have been on TB treatment for 30 or more days

Sponsors & Collaborators

• University of Stellenbosch: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (1)

Stellenbosch University

Cape Town, Western Cape, 7505, South Africa

Location

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood will be collected for transcriptional profiling after ribonucleic acid (RNA) isolation. Nasopharyngeal swab samples will be collected for comprehensive characterization of respiratory pathogens. Sputum will be collected for microbiological testing for TB with Xpert MTB/RIF Ultra and/or MGIT960 liquid culture.

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Anna Okunola, PhD

  University of Stellenbosch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 15, 2022
• Study Start: June 23, 2022
• Primary Completion: May 31, 2025
• Study Completion: December 1, 2025
• Last Updated: December 16, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be shared one year after study completion.
• Access Criteria: Anyone who is interested in accessing the data can communicate with Dr Anna Okunola via email (annaojo@sun.ac.za) and they will be given access to anonymise data upon reasonable request, after the publication of the main study manuscript. The applicant will also need to sign a Data Transfer Agreement (DTA) with Stellenbosch University.

Locations

ZA (1)