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Discovery and Qualification of TB Surrogate Markers of Treatment


EMSL Project ID
49581

Abstract

The research goal is to develop a blood-based, quantitative, biomarker assay panel using a proven, high sensitivity, multiplexed electrochemiluminescence platform that can in combination with clinical data supplant 2-month sputum culture, the current dichotomous Phase 2 trial endpoint. Identification and validation of the assay panel will take advantage of serum samples and associated clinical, radiographic, microbiologic, pharmacokinetic (PK) and pharmacodynamics (PD) data obtained from well characterized patients with culture-confirmed pulmonary TB enrolled in four studies: three CDC-funded, TB Trials Consortium (TBTC) randomized, Phase 2 clinical trials and one FDA-funded repository linked to Phase 3 TB trials. To achieve the program goal, we propose the following specific aims:
Aim 1: Identify blood-based, serum/plasma markers of treatment response for TB
which will employ an unbiased proteomics approach using Next Generation Proteomics Liquid Chromatography/Mass Spectrometry (LC/MS) Platforms to identify serum biomarkers that change in response to treatment.
Aim 2: Develop multi-parameter biomarker-based classifiers for two month culture status, treatment failure and change in time to detection of M. tuberculosis (M.tb) in liquid culture media on treatment.
Aim 3: Demonstrate utility of a prototype ECL panel and associated multi-parameter biomarker-based classifiers against independent sample sets, and once a biomarker panel is validated, design-lock the focused assay panel of surrogate markers of treatment response for TB.

Project Details

Start Date
2016-10-07
End Date
2019-09-30
Status
Closed

Team

Principal Investigator

Jon Jacobs
Institution
Environmental Molecular Sciences Laboratory

Co-Investigator(s)

Aaron Wright
Institution
Pacific Northwest National Laboratory

Related Publications

Kedia K., J.P. Wendler, E.M. Baker, K.E. Burnum-Johnson, L.G. Jarsberg, K.G. Stratton, and A.T. Wright, et al. 2018. "Application of multiplexed ion mobility spectrometry towards the identification of host protein signatures of treatment effect in pulmonary tuberculosis." Tuberculosis 112. PNNL-SA-137966. doi:10.1016/j.tube.2018.07.005
Sigal G.B., M. Segal, A. Mathew, L.G. Jarlsberg, M. Wang, S. Barbero, and N. Small, et al. 2017. "Biomarkers of Tuberculosis Severity and Treatment Effect: A Directed Screen of 70 Host Markers in a Randomized Clinical Trial." Ebiomedicine 25. PNNL-SA-129994. doi:10.1016/j.ebiom.2017.10.018