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…
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 and creatinine kinase levels
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.
Secondary outcome
Not applicable
Background summary
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.
Study 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 burden and risks
Malignant hyperthermia and rhabdomyolysis are severe and potential life
threatening medical conditions. Recent studies show growing evidence for
multisystem involvement of RYR1 variants associated with malignant
hyperthermia. In parallel, next generation sequencing has identified a rapidly
expanding number of RYR1 variants with uncertain pathogenicity based on
segregation analysis and prediction models. Knowledge about multisystem
involvement of RYR1 variants may be used for future counselling and informing
patients, future development of new research and/or treatment strategies.
The effort to participate is relatively small when taking the risks of
malignant hyperthermia and rhabdomyolysis into account. One visit to the
Radboudumc will be needed, for taking blood samples, performing neurological
examination, functional assessment, history taking muscle MRI and muscle
ultrasound.
This study can be classified as a study with a negligible risk. Blood samples
will be taken through venepuncture, a procedure with only minor risks.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
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
Specific exclusion criteria for participating in the immunological part of the
study (patients excluded for the immunological part of the study can take place
in the other parts)
* 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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL72351.091.20 |