advanced fshd-com: new clinical outcome measures to evaluate non-ambulant fshd patients, a pilot study

Conditions: Facioscapulohumeral Muscular Dystrophy

Summary: facioscapulohumeral muscular dystrophy (fshd) is one of the most common adult muscular dystrophy with an estimated prevalence range of 2-7 per 100,000. the disease is characterized by slowly progressive, asymmetric muscle weakness that starts with the face and scapular muscles. it causes significant lifetime morbidity, with up to 20% of patients eventually requiring full-time wheelchair use. however, there is a large degree of clinical variability in both disease progression and severity. this makes predicting an individual's disease course difficult and has made clinical trial design challenging. the disease is caused by the aberrant expression of a normally silenced gene, dux4, which causes disease by a toxic gain-of-function. the establishment of a unifying model for the cause of fshd made it possible to develop disease-specific targeted treatments. pharmaceutical companies are actively investigating therapeutic approaches in order to knockdown or silence dux4, including the use of antisense rna oligonucleotides which is already investigated for spinal muscular atrophy, duchenne muscular dystrophy, and myotonic dystrophy. the drug development pipeline for fshd over the next 5 years looks promising but meetings with industry, advocacy groups, and fshd scientific experts have identified several gaps that need to be addressed to accelerate efficient drug development. as drugs move from preclinical testing into human trials, it is essential to validate clinical trial tools and methodologies to facilitate drug development. there is a strong need for clinical outcome measures (coms) including biomarkers, strength outcomes, functional measures and patient reported outcomes to follow disease progression and to evaluate treatment efficacy. a large international multicenter study is currently ongoing in order to validate coms in ambulant fshd patients (resolve, nct03458832). additionally, nice university hospital is conducting an ancillary study (ctrl fshd france, nct04038138) to evaluate muscle mri, an additional emerging biomarker, to follow disease progression in the same patient population. to limit patient heterogeneity, only ambulant fshd patients are included in these 2 ongoing studies. it is therefore important to generate data in severely affected non-ambulant fshd patients, in order to validate coms that are adapted to this specific subgroup of patients for future therapeutic trials.


Eligibility criteria:
inclusion criteria: * genetically confirmed fshd1 or clinical diagnosis of fshd with characteristic findings on exam and an affected parent or offspring * age 18-75 years * symptomatic limb weakness * fshd patients who use the wheelchair daily and are able to stand or to walk at most 30 meters with assistance, and wheelchair-bound patients who are unable to walk. * clinical severity score (css) ≥ 8 * patient affiliated to the social security system * patient giving written consent after written and oral information. * if taking over the counter supplements, willing to remain consistent with supplement regimen throughout the course of the study exclusion criteria: * patients with comorbidity not related to the disease that can modify the natural evolution of the disease or would interfere with safe testing in the opinion of the investigator * regular use of available muscle anabolic/catabolic agents such as corticosteroids, oral testosterone or derivatives, or oral beta agonists * use of an experimental drug in an fshd clinical trial within the past 30 days * pregnancy * vulnerable person (person deprived of their administrative and legal liberty, hospitalized person for other purposes than research)