A Natural History Study of RYR1-Related Disorders
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age7-100
SponsorNational Institutes of Health Clinical Center (CC)
About this trial
Background:
Congenital myopathies (CM) are genetic disorders that can cause decreased muscle tone and muscle weakness. Most CMs in the United States are related to the ryanodine receptor 1 (RYR1) gene. Researchers need more natural history data to learn about these CMs in children and adults.
Objective:
To learn more about the signs, symptoms, and course of RYR1-related disorders.
Eligibility:
People aged 7 years and older with an RYR1-related disorder.
Design:
Ambulatory participants will come to the Clinical Center and non-ambulatory participants will visit via telehealth.
Visits will be once a year for 3 or 5 years. Clinical Center visits will take 2 to 3 days.
All participants will undergo tests including:
Photos and videos. These will be taken to document the participant s condition.
Blood and urine tests.
Activity Tracker. Participants will wear a device to record their activity.
Questionnaires. Participants will answer questions about their health, pain, fatigue, stress, quality of life, and other topics.
Participants who visit the Clinical Center will also undergo:
Tests of heart and lung function.
Motor skills and strength tests. Participants will walk, climb stairs, kneel, crawl, stand up, and perform other movements to test their strength and abilities. They will squeeze and pinch a handheld device to test their grip.
Imaging scans.
Skin biopsy. Adult participants may opt to have a sample of skin taken (one time only).
Eye exam
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
(CENTRALIZED ARM)
Stated willingness to comply with all study procedures, availability for the duration of the study, and submission of medical records to research team prior to screening.
Male or female, aged >=7 years of age.
Genetically confirmed RYR1-related disorder, evidenced by pathogenic or likely pathogenic variants identified by CLIA testing (whole genome, exome, targeted, partial or full RYR1 sequencing) OR variant of uncertain significance with supporting clinical phenotype.
Disqualifiers
Participation in an IND, IDE, or equivalent clinical study in the past six months
Severe disability or mobility issues (inability to walk 10 meters with or without assistance)
Requires mechanical ventilation or tracheotomy
Other neuromuscular diseases resulting in muscle weakness
Trial population
A total of 150 clinically stable adults and children (7 years of age or older) with genetically confirmed RYR1-RD.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
150 Participants
are grouped into 2 trial groupsGroup A: Centralized
Group B: Decentralized
Trial outcomes
Primary outcomes
1
Adverse and disease-related events
Serious (21CFR312.32) adverse events:- Narrative description (clinician)- Causality assessment (related or unrelated to disease)- CTCAE system organ class- CTCAE lower-level term- Falls questionnaire; adults
Time frame
3 years2
Medical data review
\- Demographics- Developmental history- Medical history- Social determinants of health (environmental conditions such as economic stability, health care and education access and quality, neighborhood and built environment, and social and community context.- Full physical exam- Review of genetic diagnostic report/results- Prior medical records
Time frame
3 years3
Ophthalmology
\- Marginal reflex distance (Ptosis)- Binocular horizontal visual field test- Optical Coherence Tomography- Goldmann Perimetry Degrees: lateral rectus, superior rectus, inferior oblique, medial rectus, superior oblique, inferior rectus
Time frame
3 years4
Patient-reported outcomes
\- PROMIS-57 Profile (subscale and overall t-scores); adults - depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and satisfaction with participation in social roles- PROMIS Ped-25 Profile (subscale and overall t-scores); 8 - 17 y- PROMIS Parent Proxy 25 Profile - Fatigue, physical stress experiences, positive affect and wellbeing, psychological stress experiences, anxiety/fear, physical function, pain; 5 - 7 y- PROMIS Upper Extremity - Short Form 7a- PROMIS Pediatric Upper Extremity - Short Form 8a- PROMIS Parent Proxy Upper Extremity - Short Form 8a- Physical Activity Questionnaire for Children (PAQ-C); 8 - 13 y- Physical Activity Questionnaire for Adolescents (PAQ-A); 14 - 17 y- International physical activity questionnaire (IPAQ); adults
Time frame
3 yearsSecondary outcomes
1
Characterize phenotype and disease course over an extended (2-year) period (total 5 years).Collect exploratory biomarker data.
(1) Investigate potential biomarkers of disease status and progression(2) Explore clinical meaningfulness thresholds for research assessments(3) Extract common data elements from existing medical records (real-world evidence)
Time frame
5 yearsSponsors and contacts
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Source ClinicalTrials.gov