A natural history study to track brain and spinal cord changes in individuals with Friedreich’s ataxia: TRACK-FA study protocol
Author:
Georgiou-Karistianis NellieORCID, Corben Louise A., Reetz Kathrin, Adanyeguh Isaac M., Corti Manuela, Deelchand Dinesh K., Delatycki Martin B., Dogan Imis, Evans Rebecca, Farmer Jennifer, França Marcondes C., Gaetz William, Harding Ian H., Harris Karen S., Hersch Steven, Joules Richard, Joers James J.ORCID, Krishnan Michelle L., Lax Michelle, Lock Eric F., Lynch David, Mareci Thomas, Muthuhetti Gamage Sahan, Pandolfo Massimo, Papoutsi Marina, Rezende Thiago J. R., Roberts Timothy P. L., Rosenberg Jens T.ORCID, Romanzetti Sandro, Schulz Jörg B., Schilling Traci, Schwarz Adam J., Subramony Sub, Yao Bert, Zicha Stephen, Lenglet Christophe, Henry Pierre-Gilles
Abstract
Introduction
Drug development for neurodegenerative diseases such as Friedreich’s ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers of pharmacodynamic response in affected tissue and disease progression. Studies employing neuroimaging measures to track FRDA have thus far been limited by their small sample sizes and limited follow up. TRACK-FA, a longitudinal, multi-site, and multi-modal neuroimaging natural history study, aims to address these shortcomings by enabling better understanding of underlying pathology and identifying sensitive, clinical trial ready, neuroimaging biomarkers for FRDA.
Methods
200 individuals with FRDA and 104 control participants will be recruited across seven international study sites. Inclusion criteria for participants with genetically confirmed FRDA involves, age of disease onset ≤ 25 years, Friedreich’s Ataxia Rating Scale (FARS) functional staging score of ≤ 5, and a total modified FARS (mFARS) score of ≤ 65 upon enrolment. The control cohort is matched to the FRDA cohort for age, sex, handedness, and years of education. Participants will be evaluated at three study visits over two years. Each visit comprises of a harmonized multimodal Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) scan of the brain and spinal cord; clinical, cognitive, mood and speech assessments and collection of a blood sample. Primary outcome measures, informed by previous neuroimaging studies, include measures of: spinal cord and brain morphometry, spinal cord and brain microstructure (measured using diffusion MRI), brain iron accumulation (using Quantitative Susceptibility Mapping) and spinal cord biochemistry (using MRS). Secondary and exploratory outcome measures include clinical, cognitive assessments and blood biomarkers.
Discussion
Prioritising immediate areas of need, TRACK-FA aims to deliver a set of sensitive, clinical trial-ready neuroimaging biomarkers to accelerate drug discovery efforts and better understand disease trajectory. Once validated, these potential pharmacodynamic biomarkers can be used to measure the efficacy of new therapeutics in forestalling disease progression.
Clinical trial registration
ClinicalTrails.gov Identifier: NCT04349514.
Funder
Friedreich's Ataxia Research Alliance Takeda Pharmaceutical Company PTC Therapeutics Novartis Pharmaceuticals Corporation IXICO plc
Publisher
Public Library of Science (PLoS)
Subject
Multidisciplinary
Cited by
2 articles.
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