Malignant Hyperthermia, Rhabdomyolysis, RYR1 Variant
Conditions
Brief summary
Rationale: Malignant hyperthermia and rhabdomyolysis are phenotypes that have long been considered to occur only in response to external stimuli (trigger anaesthesia and physical exhaustion) show several features of a continuous disease manifestation. Previous studies showed prolonged bleeding time after injury, selective immunological advantages, axial muscle weakness and several social difficulties. A detailed study of the neuromuscular and multisystem features of patients with RYR1-related malignant hyperthermia or rhabdomyolysis is needed to provide clarification about the continuous and multisystem disease manifestations in these patients. Objective: Primary Objective: There are three primary objectives in this study. 1. To investigate the neuromuscular involvement of RYR1 related MH and rhabdomyolysis. 2. To investigate the immunological changes in subjects with RYR1 related MH and rhabdomyolysis. 3. To identify multisystem features of RYR1 related MH and rhabdomyolysis. There are no secondary objectives. Study design: The design of the study will be a clinical, open, observational study. The study consists of three parts; a clinical, imaging and immunological part. Study population: Patients with a history of malignant hyperthermia susceptibility (MHS), and/or a history of rhabdomyolysis related to a variant in RYR1. Intervention (if applicable): Not applicable. Main study parameters/endpoints: The study consists of three parts. Each part has it's own main study parameters 1. Clinical part: the results of the questionnaire study compared to standardizes normal values and the results of the comprehensive clinical assessment. 2. Imaging part: fatty infiltration and hypertrophy of proximal and axial muscles. 3. Immunological part: circulating and leukocyte released anti- and pro-inflammatory cytokine levels compared to healthy age and sex matched controls.
Interventions
OTHERImmunological challenge
In vitro immunological study of subjects with RYR1 related MH/rhabdomyolysis. Studying of circulating cytokines and cytokines production after in vitro stimulation
Sponsors
Canisius-Wilhelmina Hospital
Radboud University Medical Center
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* A history of malignant hyperthermia susceptibility (MHS), confirmed by diagnostic RYR1 variant or IVCT, related to a RYR1 variant and/or a history of rhabdomyolysis related to a variant in RYR1 * Minimum age 18 years old.
Exclusion criteria
* Patients diagnosed with a neuromuscular disease resulting in muscle weakness (apart from RYR1 related rhabdomyolysis and malignant hyperthermia). * Patients with symptoms of angina pectoris. * Patients with contra-indications for MRI-scan are excluded. Contra-indications for MRI-scan include metallic implants (vascular clips, foreign bodies like metallic splinters in the eye, coronary and peripheral artery stents, prosthetic heart valves, pacemakers and ICD's, cochlear implants, breast tissue expanders and some other electronic implants or devices and known claustrophobia. * Current malignancy * Pregnancy or lactating * Other health issues whereby patients are not able to fulfil the study protocol * No written informed consent by the patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To investigate the multisystem features of RYR1 related MH and rhabdomyolysis | Directly after inclusion, subjects will fulfil a questionnaire study. | All subject will fulfil a questionnaire study, it will focus on pain, activity and psychological aspects. |
| To investigate the neuromuscular involvement of RYR1 related MH and rhabdomyolysis | Directly after inclusion, a muscle MRI's and ultra sounds will be made of all subjects. | All subjects will have a total body muscle MRI and muscle ultra sound once |
| To investigate the immunological changes in subjects with RYR1 related MH and rhabdomyolysis. | Directly after inclusion blood samples will be taken for immunological studies. | Peripheral mononuclear blood cells will be isolated and in vitro challenged using pathogens and stimulatia. The results of this part of the study will be compared to healthy controls. |
Countries
Netherlands
Outcome results
None listed