Malignant HyperthermiaNCT04610619
Multisystem Features of Malignant Hyperthermia or Rhabdomyolysis Related to RYR1 Variants
An observational study of Malignant Hyperthermia and Rhabdomyolysis, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Malignant Hyperthermia, Rhabdomyolysis, RYR1 Variant
- What is being tested?
- Immunological challenge
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- 19 Aug 2020to Jan 2022
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with RYR1 related malignant hyperthermia/rhabdomyolysis
Who may be able to join
- 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.
Who cannot join
- 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
Show all 22Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
RUniversity
Nijmegen
Luuk van den Bersselaar, M.D. MSc, +31 24 361 1111, luuk.vandenbersselaar@radboudumc.nl
About this study
Official title: The Neuromuscular and Multisystem Features of RYR1-related Malignant Hyperthermia and Rhabdomyolysis - a Study Protocol
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:
Read more
Primary Objective: There are three primary objectives in this study.
- To investigate the neuromuscular involvement of RYR1 related MH and rhabdomyolysis.
- To investigate the immunological changes in subjects with RYR1 related MH and rhabdomyolysis.
- 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
- Clinical part: the results of the questionnaire study compared to standardizes normal values and the results of the comprehensive clinical assessment.
- Imaging part: fatty infiltration and hypertrophy of proximal and axial muscles.
- 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
- Being tested
- Immunological challenge
- Medical subject headings
- Malignant Hyperthermia, Rhabdomyolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunological challengeOther
In vitro immunological study of subjects with RYR1 related MH/rhabdomyolysis. Studying of circulating cytokines and cytokines production after in vitro stimulation
| Study group | Role | What they receive |
|---|---|---|
| RYR1 related malignant hyperthermia/rhabdomyolysis | Not described Receives: Other: Immunological challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Directly after inclusion blood samples will be taken for immunological studies.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2020
- Study start19 Aug 2020
- Primary completionJan 2022 (estimated)
- Study completionJan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant HyperthermiaStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Canisius-Wilhelmina Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04610619
- Sponsor's protocol ID
- NL72351.091.20
- Status last verified
- Jul 2020
- First submitted
- 17 Jul 2020
- Last updated
- 28 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study protocol will be shared with other researchers
Publications
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.
PubMed 34414986
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Neuromuscular and Multisystem Features of RYR1-related Malignant Hyperthermia and Rhabdomyolysis - a Study Protocol
- ClinicalTrials.gov ID
- NCT04610619
- Acronym / sponsor ID
- NL72351.091.20
- Conditions
- Malignant Hyperthermia, Rhabdomyolysis, RYR1 Variant
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Canisius-Wilhelmina Hospital
- Study start
- 19 Aug 2020 (actual)
- Primary completion
- Jan 2022 (estimated)
- Study completion
- Jan 2022 (estimated)
- First posted
- 30 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- To investigate the neuromuscular involvement of RYR1 related MH and rhabdomyolysis.
- To investigate the immunological changes in subjects with RYR1 related MH and rhabdomyolysis.
- 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
- Clinical part: the results of the questionnaire study compared to standardizes normal values and the results of the comprehensive clinical assessment.
- Imaging part: fatty infiltration and hypertrophy of proximal and axial muscles.
- Immunological part: circulating and leukocyte released anti- and pro-inflammatory cytokine levels compared to healthy age and sex matched controls.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Year
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RYR1 related malignant hyperthermia/rhabdomyolysis | – | Other: Immunological challenge |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with RYR1 related malignant hyperthermia/rhabdomyolysis
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immunological challengeIn vitro immunological study of subjects with RYR1 related MH/rhabdomyolysis. Studying of circulating cytokines and cytokines production after in vitro stimulation | Other | RYR1 related malignant hyperthermia/rhabdomyolysis |
Primary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2021.
- Derived from this study: PubMed 34414986van 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.
- Individual participant dataSharing planned: Yes. The study protocol will be shared with other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malignant Hyperthermia and Rhabdomyolysis, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04610619, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2021.