Multisystem Features of Malignant Hyperthermia or Rhabdomyolysis Related to RYR1 Variants

Title: 
Multisystem Features of Malignant Hyperthermia or Rhabdomyolysis Related to RYR1 Variants
Recruitment Status: 
Status Last Updated: 
October 30, 2020
Gene(s): 
Study Purpose: 

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.

Intervention/Treatment: 
Immunological challenge
Study Description: 

n/a

Study Type: 
Official Title: 
Study of the Neuromuscular and Multisystem Features of Patients With Malignant Hyperthermia or Rhabdomyolysis Related to RYR1 Variants
Study Start Date: 
August 19, 2020
Study Completion Date: 
January 2022
Primary Objective(s): 

To investigate the neuromuscular involvement of RYR1 related MH and rhabdomyolysis [ Time Frame: 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 multisystem features of RYR1 related MH and rhabdomyolysis [ Time Frame: 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 multisystem features of RYR1 related MH and rhabdomyolysis [ Time Frame: Six months 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 multisystem features of RYR1 related MH and rhabdomyolysis [ Time Frame: Twelve months 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 immunological changes in subjects with RYR1 related MH and rhabdomyolysis. [ Time Frame: 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.

Secondary Objective(s): 

n/a

Eligibility: 

Ages Eligible for Study:      18 Years and older   (Adult, Older Adult)

Sexes Eligible for Study:      All

Accepts Healthy Volunteers:      Yes

Sampling Method:      Probability Sample

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

Exclusion criteria for immunological part of the study:

Diabetes mellitus

Patients currently using medicine affecting the immune system.

Patients with a compromised immunity (e.g. HIV)• Patients with a history of auto-immune disease (e.g. SLE, psoriasis, IBD)

Use of statins the past year

Use of systemic corticosteroids during more than two weeks in the past 5 years

Previous treatment with chemotherapy and/or radiation therapy

Age > 65 years old.

Exclusion criteria for healthy controls

History of malignant hyperthermia

Variant in RYR1

A RYR1 related myopathy

History of heat stroke

History of rhabdomyolysis

Family history of malignant hyperthermia or a RYR1 variant

Family history of inexplicable perioperative dead

Family history of a RYR1 related myopathy

Study Site(s)/Location(s): 



Netherlands

RUniversity    Recruiting

Nijmegen, Netherlands

Contact: Luuk van den Bersselaar, M.D. MSc    +31 24 361 1111    luuk.vandenbersselaar@radboudumc.nl   

Sponsors & Collaborators: 

Radboud University

Canisius-Wilhelmina Hospital

Principal Investigator(s): 

n/a

For more information, please contact the Study Coordinator: 

Contact:  

Email: 

Phone: 

ClinicalTrials.gov ID: 
NCT04610619