Multisystem Features of Malignant Hyperthermia or Rhabdomyolysis Related to RYR1 Variants

NCT ID: NCT04610619

Last Updated: 2021-07-28

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-08-19
• Study Completion Date: 2022-01-31

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.

Conditions

Malignant Hyperthermia; Rhabdomyolysis; RYR1 Variant

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

RYR1 related malignant hyperthermia/rhabdomyolysis

Immunological challenge

Intervention Type: OTHER

In vitro immunological study of subjects with RYR1 related MH/rhabdomyolysis. Studying of circulating cytokines and cytokines production after in vitro stimulation

Interventions

Immunological challenge

In vitro immunological study of subjects with RYR1 related MH/rhabdomyolysis. Studying of circulating cytokines and cytokines production after in vitro stimulation

Intervention Type: OTHER

Eligibility Criteria

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

• 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.

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Canisius-Wilhelmina Hospital

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

RUniversity

Nijmegen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Facility Contacts

Luuk van den Bersselaar, M.D. MSc

Role: primary

luuk.vandenbersselaar@radboudumc.nl

+31 24 361 1111

References

van den Bersselaar LR, Kruijt N, Scheffer GJ, van Eijk L, Malagon I, Buckens S, Custers JA, Helder L, Greco A, Joosten LA, van Engelen BG, van Alfen N, Riazi S, Treves S, Jungbluth H, Snoeck MM, Voermans NC. The neuromuscular and multisystem features of RYR1-related malignant hyperthermia and rhabdomyolysis: A study protocol. Medicine (Baltimore). 2021 Aug 20;100(33):e26999. doi: 10.1097/MD.0000000000026999.

Reference Type: DERIVED

PMID: 34414986 (View on PubMed)

Other Identifiers

NL72351.091.20

Identifier Type: -

Identifier Source: org_study_id