New Clinical Outcome Measures to Remotely Evaluate Patients With FacioScapuloHumeral Muscular Dystrophy

Study Overview
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Brief Summary
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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 and the development of new therapeutic strategies challenging. The disease is caused by the aberrant expression of a normally silenced gene, Double homeobox 4 (DUX4), which causes disease by a toxic gain-of-function. The emergence of the pathophysiologic model provided several possible therapeutic approaches to treat FSHD. However, as drugs move from preclinical testing into human trials, it is essential to validate clinical trial tools and methodologies to facilitate drug development from early phase studies through registration trials. Natural history studies are conducted to develop and validate new clinical outcome measures (COMs). 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 (CTRN FSHD France, NCT04038138) to evaluate muscle MRI, an additional emerging biomarker, to follow disease progression in the same patient population. Nevertheless, these studies are focused on the development of COMs collected at the hospital. In this setting, several factors that may interfere with disease progression or patient quality of life are underestimated (daily exercise, daily pain or fatigue, the psychological impact of the disease, and falls…). Consequently, and given the context of the current pandemic, the interest of pharmaceutical companies, stakeholders, clinicians, and researchers in data collected in a cohort of FSHD patients at home is rapidly increasing. Consequently, a new battery of COMs adapted for the remote evaluation needs to be developed and/or validated. There are clear benefits to remote assessments. The ability to observe an individual perform functional mobility tasks and self-care in their natural environment is meaningful and invaluable. The set-up of a reliable remote assessment will allow for ensuring drug home delivery, maintaining patients on trials, and collecting and analysing additional data to improve patient stratification in clinical trials and develop new approaches to assess the short-term and long-term efficacy of a given therapy. Remote assessment can also be the key to developing more efficient real-life studies, empowering patients and caregivers in the management of this disease, and more efficiently monitoring drug side effects or the socio-economic burden of the disease. The overall aim of the PROGRESS FSHD study is to experiment the feasibility of the remote evaluation in patients with FSHD, through the use of a patient-oriented mobile application (myFSHD app). The content of the application has been determined after extensive discussions with patients and patients' associations that have identified their unmet needs and based on preliminary results of the CTRN FSHD France project. The video-recorded exercises have been designed specifically to stress a particular body region. The myFSHD mobile application will be used by 70 FSHD1 patient during 12 months, at home and at the hospital, to administer patient-reported questionnaires on fatigue, pain, physical activity, sleep, quality of life, and socio-economic burden of the disease, as well as video of validated scores and scales. The collected data will help to: Evaluate patients' adherence to the program Evaluate the technical feasibility of remote evaluation Assess the reliability of remote evaluation Assess the robustness of new COMs compared to commonly used COMs Evaluate the quality of life and socio-economic burden of the disease Overall, this study will provide digital tools adapted to monitor disease evolution remotely in FSHD patients. The patient-generated measures collected through connected digital tools (patient full-body motion videos collected through the myFSHD app) can be used to explain, influence, and/or predict disease-related outcomes

Official Title
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New Clinical Outcome Measures to Remotely Evaluate Patients With FacioScapuloHumeral Muscular Dystrophy - PROGRESS FSHD

Conditions
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Type 1 Facioscapulohumeral Muscular Dystrophy

Intervention / Treatment
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* Other: Remote monitoring program


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Genetically confirmed FSHD1 or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring (40) Age 18-75 years Symptomatic limb weakness Patient able to walk alone or with a walking aid. 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 Non inclusion 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 Pregnant or nursing women for women of childbearing age Patient protected by law, under guardianship or curator ship, or not able to participate in a clinical study according to the article L.1121-16 of the French Public Health Code

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Patient with type 1 facioscapulohumeral muscular dystrophy<br> | Other: Remote monitoring program<br>* Remote program is composed of some questionnaires and physical exercises performed at home and at hospital (depending on the concerned visit)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the patients' adherence to the program, with the mobile application, over 12 months | The adherence to the program will be evaluated based on the number of times a patient has performed a task without a reminder from the medical team compare to the number of total tasks to perform. | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the global technical feasibility of remote assessment, using digital clinical outcome measures (COMs), in ambulant FSHD1 patients, over 12 months, from health care providers' perspective | The technical feasibility, from the physician perspective will be evaluated using a feasibility questionnaire containing several items, such as quality of the videos, completeness of the questionnaires, data storage and data transmission. This questionnaire will be filled every 6 months by the physician. Each item will be evaluated using a 2-point Likert scale, with two options (yes and no). The percentage of questionnaires with a score of 4/4 will be calculated and the overall technical feasibility from the physician's perspective will be achieved if at least 50% of the questionnaires have received a score of 4/4. | up to 12 months | 
| Evaluate the global technical feasibility of remote assessment, using digital clinical outcome measures (COMs), in ambulant FSHD1 patients, over 12 months, from patients' perspective | The technical feasibility, from the patient's perspective will be evaluated using a feasibility questionnaire containing several items, such as visibility, ease to use, clarity, stability, satisfaction. Each item will be evaluated using a 10-point Likert scale ranging from 1 to 10. Each individual score will be added to obtain a total sum score for the questionnaire. We will then calculate the total mean of all questionnaires and consider that the overall technical feasibility from the patients' perspective has been achieved if the total mean is at least 6/10. | up to 12 months |