digital biotyping of fshd patients and controls

Conditions: Muscular Dystrophy, Facioscapulohumeral

Summary: facioscapulohumeral muscular dystrophy (fshd) is a devastating progressive muscle dystrophy. there is no treatment. fshd is generally characterized by asymmetrical weakness and wasting of facial, shoulder girdle and upper arm muscles followed by weakness of muscles of the trunk and lower extremities, but disease severity varies widely between patients. relatively long periods of stability are interspersed with short periods of potentially steep decline, leading overall to a slow but unpredictable rate of progression. different genotypes underlying fshd have been identified, but they result in highly similar phenotypes and at the molecular level converge on undue expression of the transcription factor, dux4, in skeletal muscle, which is thought to (ultimately) lead to muscle wasting due to inflammation, apoptosis, and oxidative stress. there is no approved treatment, although various companies are engaged in fshd drug discovery and development aimed in particular at reducing dux4 expression. multiple treatment options are currently under development in both preclinical and early clinical stages. however, these efforts face significant challenges in the path to regulatory approval. because of the slow and variable rate of progression of fshd, evidencing a significant treatment response will be cumbersome using only the existing measurements of muscle function. the successful development of these investigative treatments for fshd is therefore highly dependent on the availability of validated disease and treatment biomarkers to monitor disease progression and response to treatment, respectively. to date, no such validated biomarkers exist. this study is important for four reasons: 1. clinical testing of fshd drug candidates requires the availability of clinical biomarkers that (a) change relatively rapidly over time; (b) allow for identification of fast progressors; and (c) correlate with "gold standard", but slowly changing, clinical severity and/or functional scores. this study is a first step in that direction as it seeks to explore if the investigational digital technologies described below are able to generate single or composite variables that (cross-sectionally) distinguish fshd patients from controls. if identified, such variables will be tested as putative clinical fshd biomarkers in a follow-up longitudinal study with fshd patients. 2. patient testimonies indicate that living with fshd means living with pain, fatigue, social isolation, and anxiety about the future. this study provides the first-ever opportunity to gather objective, real-world data about the impact of fshd on daily life. 3. regulators have already indicated that real-world data (rwd) is a top strategic priority for their drug reviews. this study aims to fill this gap by gathering rwd about the physical and social activities of fshd patients in comparison with controls. this way we aim to find (composite) scores that correlate with selected severity and functional scores and additionally distinguish fshd patients from controls. 4. this study offers an opportunity to expand the spectrum of diseases in which rwd may be used as (a basis for) clinical outcome measures. a successful outcome of this study may support testing the more platform in other muscular dystrophies as well.


Eligibility criteria:
inclusion criteria: patients eligible for inclusion in this study have to fulfill all of the following criteria: 1. written informed consent is obtained before any assessment is performed. 2. males and females age 16+ years. 3. genetically confirmed fshd. 4. symptomatic as demonstrated by lamperti score \>0. 5. fully functioning android-based smartphone with android version 5.0 or higher. 6. able to comply with the study procedures, prohibitions and restrictions (drug use) as specified in the protocol. controls inclusion criteria controls eligible for inclusion in this study have to fulfill all of the following criteria: 1. written informed consent is obtained before any assessment is performed. 2. males and females age 16+ years. 3. unrelated subjects without fshd. 4. fully functioning android-based smartphone with android version 5.0 or higher. 5. able to comply with the study procedures, prohibitions and restrictions (drug use) as specified in the protocol. exclusion criteria: patients fulfilling any of the following criteria are not eligible for inclusion in this study: 1. current or previously diagnosed illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study. 2. positive urine β-human chorionic gonadotropin (β-hcg) pregnancy test at screening in women of childbearing potential. 3. wearing a pacemaker or other internal medical device (e.g. vagus nerve stimulation (vns), deep brain stimulation (dbs)). 4. current enrollment in an interventional study. controls fulfilling any of the following criteria are not eligible for inclusion in this study: 1. current or previously diagnosed illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study. 2. positive urine β-human chorionic gonadotropin (β-hcg) pregnancy test at screening in women of childbearing potential. 3. wearing a pacemaker or other internal medical device (e.g. vagus nerve stimulation (vns), deep brain stimulation (dbs)). 4. current enrollment in an interventional study.

Keywords: facioscapulohumeral muscular dystrophy biotyping