An Observational Study in Participants with Ryanodine Receptor 1-Related Myopathies (RYR1-RM) to Determine Optimal Endpoint Measurements.

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

- Males and females aged 18 years and older at screening;
- Confirmed genetic diagnosis of RYR1-RM with autosomal dominant mutation and
supporting clinical phenotype with demonstrable proximal weakness on at least
one of the baseline study assessments;
- Evidence of at least one demonstrable muscle/motor function deficit assessed
through Manual muscle Testing (MMT) and scored using the medical Research
Council (MRC) Scale for muscle strength on physical examination;
- Able to walk 10 meters, with or without assistance - e.g. with a cane
(assessed using the 10 Meter Walk Test);
- Willingness and ability to comply with scheduled visits and study procedures;
- Willingness to be fitted with the Syde device at Screening Visit (for
inclusion in the exploratory objective analysis only); and
- Able to provide written informed consent and understand the study procedures
in the informed consent form (ICF).

Exclusion Criteria

- Severe pulmonary dysfunction at Screening (FVC < 40% predicted) or evidence
of pulmonary exacerbation (note that pulmonary exacerbations refer to acute
worsening respiratory symptoms resulting from a decline in lung function);
- Significant cognitive impairment in the judgement of the investigator who
will be unable to follow the protocol;
- Patients with progressive neurological conditions (e.g. Parkinson's disease);
- Non-ambulant patients; or
- Pregnant woman.

Study & Design

Study Type: Observational non invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary outcome measure is muscle strength assessment and change or<br /><br>variability in muscle strength over the<br /><br>duration of the study This will be tested using multiple methods, including<br /><br>Quantitative Muscle Assessment (QMA),<br /><br>Manual Muscle Test (MMT), and Hand Held Dynamometry (HHD). Additional tests for<br /><br>measuring strength including 10<br /><br>meter walk test, 1-min sit-to-stand test and stair climb test will also be used<br /><br>in this study. Muscles to be measured are<br /><br>neck flexion, shoulder abduction, elbow flexion, knee extension and flexion<br /><br>strength. The study will essentially<br /><br>determine endpoints to take forward in further studies.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary outcomes measures include:<br />• Fatigue physical function and physical activity will be measured using PROs.<br />• Demographics and clinical characteristics (medication use including current<br />and prior medications, medical history,<br />physical, neurological, and functional exam, height, weight, BMI, and vital<br />signs)<br />• Patient symptoms will be reported using a symptom diary that will be<br />completed by patients in their own words<br />detailing their main symptom,other symptoms as well as medications they are<br />currently taking.</p>