Ryanodine receptor 1-related myopathies with autosomal dominant mutations Genetic Diseases
Conditions
Interventions
This is an observational, prospective, multi-centre study to assess muscle strength in patients with RYR1-RM with autosomal dominant mutations. The study aims to determine the optimal endpoints for th
Sponsors
RyCarma Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients (biological sex*) aged 18 years or older at Screening; Adult males and females aged 18 years and older at Screening 2. 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 3. Evidence of at least one demonstratable muscle/motor function deficit assessed through MMT and scored using the MRC Scale for muscle strength on physical examination 4. Able to walk 10 meters, with or without assistance - e.g., with a cane (assessed using the 10-MWT) 5. Willingness and ability to comply with scheduled visits, and study procedures 6. Willingness to be fitted with the Syde® device at Screening Visit (for inclusion in the exploratory objective only) 7. Able to provide written informed consent and understand the study procedures in the informed consent form (ICF)
Exclusion criteria
Exclusion criteria: Participants meeting at least one of the following criteria will not be eligible for the study: 1. 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) 2. Significant cognitive impairment in the judgement of the investigator who will be unable to follow the protocol 3. Patients with progressive neurological conditions (e.g., Parkinson’s disease) 4. Non-ambulant patients 5. Pregnant women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The following primary outcome variables will be assessed at Screening, V1, V2, and EOS: 1. Knee flexion and extension, elbow flexion and extension, and shoulder abduction measured using a quantitative muscle assessment (QMA) 2. Neck flexion measured using a hand-held dynamometer (HHD) and manual muscle test (MMT) 3. Muscle strength measured using a 10-meter walk test (10-MWT), a 1-minute sit-to-stand test, and a 4-Stair climb test The study will consist of up to four visits: 1. Screening Visit conducted at baseline 2. Visit 1 (V1: 30 ± 3 days) 3. Visit 2 (V2: 60 ± 3 days) 4. End of Study (EOS) Visit (90 ± 3 days) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Fatigue and physical function measured using the PROMIS Fatigue, PROMIS-physical function domains at Screening and EOS 2. Physical activity measured using the International Physical Activity Questionnaire (IPAQ) at Screening and EOS 3. Demographics measured using data collected in medical records at screening 4. Clinical characteristics of patients measured using data collected in medical records and full physical assessments at Screening and EOS 5. Syptoms measured using a diary at screening and EOS The study will consist of up to four visits: 1. Screening Visit conducted at baseline 2. Visit 1 (V1: 30 ± 3 days) 3. Visit 2 (V2: 60 ± 3 days) 4. End of Study (EOS) Visit (90 ± 3 days) | — |
Countries
England, France, Netherlands, United Kingdom
Contacts
Public ContactMatthew Knight
Outcome results
None listed