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Published in: BMC Neurology 1/2019

Open Access 01-12-2019 | Muscular Dystrophy | Study protocol

Clinical trial readiness to solve barriers to drug development in FSHD (ReSolve): protocol of a large, international, multi-center prospective study

Authors: Samantha LoRusso, Nicholas E. Johnson, Michael P. McDermott, Katy Eichinger, Russell J. Butterfield, Elena Carraro, Kiley Higgs, Leann Lewis, Karlien Mul, Sabrina Sacconi, Valeria A. Sansone, Perry Shieh, Baziel van Engelen, Kathryn Wagner, Leo Wang, Jeffrey M. Statland, Rabi Tawil, on behalf of the ReSolve Investigators and the FSHD CTRN18

Published in: BMC Neurology | Issue 1/2019

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Abstract

Background

Facioscapulohumeral muscular dystrophy (FSHD) is a dominantly-inherited progressive muscular dystrophy caused by de-repression of the DUX4 gene, which causes disease by a toxic-gain-of-function. As molecularly targeted drugs move from preclinical testing into human trials, it is essential that we validate clinical trial tools and methodology to facilitate the drug development process.

Methods/design

The primary goal of this study is to hasten drug development for FSHD by validating two novel clinical outcome assessments (COAs) and refining clinical trial strategies. We will perform an 18-month longitudinal study in 220 genetically confirmed and clinically affected participants using our FSHD Clinical Trial Research Network, comprised of 8 sites in the United States, and 3 collaborating sites in Europe. Visits occur at baseline and months 3, 12, and 18. At each visit we will collect: 1) a novel FSHD functional composite COA made up of 18 evaluator-administered motor tasks in the domains of shoulder/arm, hand, core/abdominal, leg, and balance function; and 2) electrical impedance myography as a novel muscle quality biomarker (US sites). Other COAs include 1) Domain 1 of the Motor Function Measure; 2) Reachable workspace; 3) orofacial strength using the Iowa Oral Performance Instrument; 4) lean muscle mass using dual-energy X-ray absorptiometry (DEXA); 5) strength as measured by quantitative myometry and manual muscle testing; and 6) the FSHD Health Index and other patient-reported outcomes. Plasma, DNA, RNA, and serum will be collected for future biomarker studies. We will use an industry standard multi-site training plan. We will evaluate the test-retest reliability, validity, and sensitivity to disease progression, and minimal clinically important changes of our new COAs. We will assess associations between demographic and genetic factors and the rate of disease progression to inform refinement of eligibility criteria for future clinical trials.

Discussion

To the best of our knowledge, this is the largest collaborative study of patients with FSHD performed in the US and Europe. The results of this study will enable more efficient clinical trial design. During the conduct of the study, relevant data will be made available for investigators or companies pursuing novel FSHD therapeutics.

Trial registration

clinicaltrials.​gov NCT03458832; Date of registration: 1/11/2018
Appendix
Available only for authorised users
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Metadata
Title
Clinical trial readiness to solve barriers to drug development in FSHD (ReSolve): protocol of a large, international, multi-center prospective study
Authors
Samantha LoRusso
Nicholas E. Johnson
Michael P. McDermott
Katy Eichinger
Russell J. Butterfield
Elena Carraro
Kiley Higgs
Leann Lewis
Karlien Mul
Sabrina Sacconi
Valeria A. Sansone
Perry Shieh
Baziel van Engelen
Kathryn Wagner
Leo Wang
Jeffrey M. Statland
Rabi Tawil
on behalf of the ReSolve Investigators and the FSHD CTRN18
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2019
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-019-1452-x

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