Multisystem Features of Malignant Hyperthermia or Rhabdomyolysis Related to RYR1 Variants

NCT04610619 | Unknown DMC

• 1 other identifier: NL72351.091.20
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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. 1.To investigate the neuromuscular involvement of RYR1 related MH and rhabdomyolysis.
2. 2.To investigate the immunological changes in subjects with RYR1 related MH and rhabdomyolysis.
3. 3.To identify multisystem features of RYR1 related MH and rhabdomyolysis.
4. 4.Clinical part: the results of the questionnaire study compared to standardizes normal values and the results of the comprehensive clinical assessment.
5. 5.Imaging part: fatty infiltration and hypertrophy of proximal and axial muscles.
6. 6.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

Outcome Measures

Primary Outcomes (5)

• To investigate the neuromuscular involvement of RYR1 related MH and rhabdomyolysis

  All subjects will have a total body muscle MRI and muscle ultra sound once

  Directly after inclusion, a muscle MRI's and ultra sounds will be made of all subjects.

• To investigate the multisystem features of RYR1 related MH and rhabdomyolysis

  All subject will fulfil a questionnaire study, it will focus on pain, activity and psychological aspects.

  Directly after inclusion, subjects will fulfil a questionnaire study.

• To investigate the multisystem features of RYR1 related MH and rhabdomyolysis

  All subject will fulfil a questionnaire study, it will focus on pain, activity and psychological aspects.

  Six months after inclusion, subjects will fulfil a questionnaire study.

• To investigate the multisystem features of RYR1 related MH and rhabdomyolysis

  All subject will fulfil a questionnaire study, it will focus on pain, activity and psychological aspects.

  Twelve months after inclusion, subjects will fulfil a questionnaire study.

• To investigate the immunological changes in subjects with RYR1 related MH and rhabdomyolysis.

  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.

  Directly after inclusion blood samples will be taken for immunological studies.

Study Arms (1)

RYR1 related malignant hyperthermia/rhabdomyolysis

Other: Immunological challenge

Interventions

Immunological challenge OTHER

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

RYR1 related malignant hyperthermia/rhabdomyolysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with RYR1 related malignant hyperthermia/rhabdomyolysis

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Canisius-Wilhelmina Hospital: collaborator

Study Sites (1)

RUniversity

Nijmegen, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 34414986 DERIVED

MeSH Terms

Conditions

Malignant Hyperthermia; Rhabdomyolysis

Condition Hierarchy (Ancestors)

Intraoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Hyperthermia; Body Temperature Changes; Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: October 30, 2020
• Study Start: August 19, 2020
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: July 28, 2021

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

NL (1)