Evaluation of Host Biomarker-based Point-of-care Tests for Targeted Screening for Active TB

Summary

Title: Evaluation of host biomarker-based point-of-care tests for targeted screening for active TB (Screen TB)

Introduction: Tuberculosis (TB) places severe pressure on health care services of the developing world. Despite the introduction of the highly sensitive and specific GeneXpert MTB/RIF (GeneXpert) test \[1\] with a potential turn-around time of two hours, many people in high TB prevalence areas still do not have access to efficient TB diagnostic services due to logistical constraints in these settings. A cost effective, rapid, point-of-care screening test with high sensitivity would identify people with a high likelihood for active TB and would prioritize them for testing with more expensive, technically or logistically demanding assays including GeneXpert or liquid culture, facilitating cost-effective diagnostic work-up in resource-limited settings. A serum cytokine signature for active TB disease, discovered in the AE-TBC project, with a sensitivity of 89% (CI 78 - 95%) and specificity of 76% (CI 68 - 83%), will be optimised and utilized in a point-of-care format (TransDot) to rapidly test for TB disease in symptomatic people.

Hypothesis: The TransDot test will achieve a sensitivity of \> 90% for TB disease, in a training set of people suspected of having TB disease, and be validated (achieve similarly high sensitivity) subsequently in a prospective test set of people suspected of having TB disease, when compared to a composite gold standard of sputum culture, smear, GeneXpert, chest X-ray, TB symptoms and TB treatment response.

Objectives: The overall objective of the study is to incorporate a six-marker serum signature into a multiplex UCP-LFA format, referred to as TransDot, for finger-prick blood testing. The end point of the study is the accuracy (sensitivity and specificity) of the UCP-LFA TransDot test on finger-prick blood for active TB and will be prospectively compared against gold standard composite diagnostic criteria (GeneXpert, MGIT culture, TB sputum smear, CXR, TB symptom screen and response to TB treatment).

Primary: The primary outcome of interest will be accuracy, sensitivity and specificity of the TransDot finger-prick test when compared with the composite gold standard tests.

Conditions

• Pulmonary Tuberculosis

Interventions

DIAGNOSTIC_TEST

Trans-Dot point-of-care test

Training set participants will be recruited and receive investigations for TB. Blood samples will also be collected from them for performance of ELISAs and laboratory-based TransDot tests. These blood samples will be drawn at baseline, week 8 and week 24 at end of treatment for confirmed TB cases and at baseline for non-TB cases. Test set participants will be recruited and receive investigations for TB. A POC TransDot test will be performed on fingerprick blood at baseline, and at week 8 and week 24 in participants on TB treatment, as well as a laboratory based TransDot test on serum at baseline. The week 8 and week 24 TransDot tests will be used to investigate the test's utility as an indicator of treatment response.

Sponsors & Collaborators

• Armauer Hansen Research Institute, Ethiopia

  collaborator OTHER

• Medical Research Council Unit, The Gambia

  collaborator OTHER

• Leiden University Medical Center

  collaborator OTHER

• Makerere University

  collaborator OTHER

• London School of Hygiene and Tropical Medicine

  collaborator OTHER

• European and Developing Countries Clinical Trials Partnership (EDCTP)

  collaborator OTHER_GOV

• LINQ Management GMBH

  collaborator UNKNOWN

• Prof Gerhard Walzl

  lead OTHER

Principal Investigators

• Gerhard Walzl, PhD, MD · Head of Department of Biomedical Sciences

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-04-01

Primary Completion

2019-04-30

Completion

2020-07-31

Countries

• Ethiopia
• Germany
• Namibia
• Netherlands
• South Africa
• The Gambia
• Uganda
• United Kingdom

Study Locations