Hyperthermia, MalignantNCT04287556
Population at Risk of Malignant Hyperthermia: Ambispective Cohort.
An observational study of Hyperthermia, Malignant, run by Instituto de Investigación Hospital Universitario La Paz at 1 site in Spain.
Trial summary
Malignant hyperthermia (MH) is a pharmacogenetic disease that manifests itself as a hypermetabolic response of skeletal musculature, in genetically susceptible patients, with the inhalation of volatile halogenated anesthetics, depolarizing neuromuscular relaxants such and, rarely, physical stressors such as intense… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hyperthermia, Malignant
- What is being tested?
- In vitro contracture test (IVCT), In vitro test of hypermetabolism in B lymphocytes and Genetic test
- How many people
- 90 participants
- Where
- 1 siteSpain
- Study dates
- 26 Feb 2020to 28 Feb 2025
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patient with hypermetabolic response of skeletal musculature by related causes in the literature with Malignant Hyperthermia.
Who may be able to join
- Patients who have suffered at least one episode of rhabdomyolysis due to related causes in the literature with susceptibility to HM.
- Patients who have been given information about the study and have agreed to sign the consent of the study. The muscle biopsy will be performed under usual clinical practice.
Who cannot join
- Patients who have suffered episodes of rhabdomyolysis due to alternative causes: trauma, compression hypoxia during immobilization or loss of consciousness or infectious arterial occlusion (influenza A and B, coxackievirus, Epstein-Barr, HIV, legionella, Streptococcus pyogenes Staphilococcus aureus, clostridium), metabolic or electrolyte abnormalities (hypokalemia, hypophosphatemia, hypocalcemia, non-ketosic hyperosmolar conditions, diabetic ketoacidosis), others.
- Children under 10 years or less than 30 kg are excluded for the in vitro test (muscle biopsy).
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitario La Paz
Madrid, 28046
Elena Ramírez García, +34 917277559, elena.ramirezg@uam.es
About this study
Malignant hyperthermia (MH) is a pharmacogenetic disease that manifests itself as a hypermetabolic response of skeletal musculature, in genetically susceptible patients, with the inhalation of volatile halogenated anesthetics, depolarizing neuromuscular relaxants such and, rarely, physical stressors such as intense exercise and heat stroke.
HM diagnosis is based on the performance of two tests:
Read more
- In vitro muscle contraction test (IVCT): it is the gold standard of the diagnosis of HM in Europe.
- Pharmacogenetic study: about 50 genetic variants associated with HM have been described.
It also has been described that B lymphocytes of patients with MH have metabolic alterations.
The main objective is to evaluate the association of disorders that occur with hypermetabolic response of skeletal musculature and susceptibility to malignant hyperthermia (MH).
Read the detailed description
Malignant hyperthermia (MH) is a pharmacogenetic disease that manifests itself as a hypermetabolic response of skeletal musculature, in genetically susceptible patients, with the inhalation of volatile halogenated anesthetics, depolarizing neuromuscular relaxants such and, rarely, physical stressors such as intense exercise and heat stroke.
Risk factors to present this disease are:
- An adverse reaction to general anesthesia manifested as an unexplained increase in carbon, dioxide production, tachycardia, temperature rise, muscle. stiffness, rhabdomyolysis, disseminated intravascular coagulation or death, or both. During anesthesia or within 60 minutes of treatment discontinuation.
- Family history of unexplained perioperative death.
- Postoperative rhabdomyolysis after clinical exclusion of other myopathies.
- Stress rhabdomyolysis, recurrent or persistent rhabdomyolysis increased serum creatine kinase concentration where no cause has been identified after neurological study (idiopathic hyperCKemia).
- Heat stroke by effort that requires hospital admission, where known predisposing factors have been excluded.
- Other myopaties Extreme physical activity, as well as environments with high temperatures favor the appearance of ischemia, anoxia and release of calcium from the sarcoplasmic reticulum, thus increasing the risk of developing MH.
There are also other infrequent diseases in which there is a ryanodine canalopathy by a mechanism similar to that seen in MH, but in cells of tissues other than skeletal striated muscle; as well as some drugs and other rare diseases that may be related to MH.
Despite the rarity of MH and given the severity of the disease clinic, it is mandatory to explore possible risks in patients with hypermetabolic response of skeletal musculature due to rare or trigger diseases (medications, drugs of abuse, exercise, extreme heat, others) whose MH risk is not defined.
Although the standard method for the diagnosis of MH is the in vitro test for halothane caffeine contraction (IVCT), it has been described that B lymphocytes of patients with MH have metabolic alterations. Alto, there are about 50 genetic variants associated with MH that have been described.
- Conditions
- Hyperthermia, Malignant
- Being tested
- In vitro contracture test (IVCT), In vitro test of hypermetabolism in B lymphocytes, Genetic test
- Medical subject headings
- Malignant Hyperthermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
In vitro contracture test (IVCT)Diagnostic test
In vitro study of muscle contraction after exposure to different substances (caffeine and halothane).
In vitro test of hypermetabolism in B lymphocytesDiagnostic test
In vitro study of the activation of lymphocytes B after being incubated with a cocktail of primary antibodies and measuring the acidification in response to the RyR1, 4-CmC agonist, using ryanodine as a positive control.
Genetic testDiagnostic test
Analysis of genes related to MH (CACNA1S and RYR1).
| Study group | Role | What they receive |
|---|---|---|
| Population in risk of MH | Patient with hypermetabolic response of skeletal musculature by causes related with Malignant Hyperthermia in the literature. Receives: Diagnostic Test: In vitro contracture test (IVCT); Diagnostic Test: In vitro test of hypermetabolism in B lymphocytes; Diagnostic Test: Genetic test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination, by an in vitro study of muscular contraction, measuring the muscle tension, of the presence of Malignant Hyperthermia susceptibility in patients with a history of hypermetabolic response of skeletal musculature.
Measured by the tension induced by the muscular contraction in response to the presence of caffeine and halothane.
Measured: 5 years
Determination, by genetic study, of the presence of susceptibility to Malignant Hyperthermia in patients with a history of hypermetabolic response of skeletal musculature.
Identifying determined genes related with Malignant Hyperthermia risk.
Measured: 5 years
Study of the concordance of the genetic study and IVCT versus the hypermetabolic response of B lymphocyte, in patients with a history of hypermetabolic response of skeletal musculature.
Extracellular acidification curve in B lymphocytes in response to the agonist RyR1 and 4-CmC.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2020
- Study start26 Feb 2020
- Primary completion28 Feb 2025 (estimated)
- Study completion28 Feb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hyperthermia, MalignantStudies of the same condition, open and under way.
- 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
- Other
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigación Hospital Universitario La Paz
- Sponsor type
- University, hospital or other
- Collaborators
- Universidad Autonoma de Madrid
- Responsible party
- Sponsor
- Investigators
- Elena Ramírez García, Principal investigator, Clinical Pharmacology Department, La Paz University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04287556
- Sponsor's protocol ID
- HUL-RHM-2019
- Status last verified
- Aug 2021
- First submitted
- 4 Feb 2020
- Last updated
- 13 Jan 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Population at Risk of Malignant Hyperthermia: Ambispective Cohort.
- ClinicalTrials.gov ID
- NCT04287556
- Acronym / sponsor ID
- HUL-RHM-2019
- Conditions
- Hyperthermia, Malignant
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Instituto de Investigación Hospital Universitario La PazUniversity, hospital or other
- Collaborators
- Universidad Autonoma de Madrid
- Study start
- 26 Feb 2020 (actual)
- Primary completion
- 28 Feb 2025 (estimated)
- Study completion
- 28 Feb 2025 (estimated)
- First posted
- 27 Feb 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.
Malignant hyperthermia (MH) is a pharmacogenetic disease that manifests itself as a hypermetabolic response of skeletal musculature, in genetically susceptible patients, with the inhalation of volatile halogenated anesthetics, depolarizing neuromuscular relaxants such and, rarely, physical stressors such as intense exercise and heat stroke.
HM diagnosis is based on the performance of two tests:
- In vitro muscle contraction test (IVCT): it is the gold standard of the diagnosis of HM in Europe.
- Pharmacogenetic study: about 50 genetic variants associated with HM have been described.
It also has been described that B lymphocytes of patients with MH have metabolic alterations.
The main objective is to evaluate the association of disorders that occur with hypermetabolic response of skeletal musculature and susceptibility to malignant hyperthermia (MH).
Detailed description
Malignant hyperthermia (MH) is a pharmacogenetic disease that manifests itself as a hypermetabolic response of skeletal musculature, in genetically susceptible patients, with the inhalation of volatile halogenated anesthetics, depolarizing neuromuscular relaxants such and, rarely, physical stressors such as intense exercise and heat stroke.
Risk factors to present this disease are:
- An adverse reaction to general anesthesia manifested as an unexplained increase in carbon, dioxide production, tachycardia, temperature rise, muscle. stiffness, rhabdomyolysis, disseminated intravascular coagulation or death, or both. During anesthesia or within 60 minutes of treatment discontinuation.
- Family history of unexplained perioperative death.
- Postoperative rhabdomyolysis after clinical exclusion of other myopathies.
- Stress rhabdomyolysis, recurrent or persistent rhabdomyolysis increased serum creatine kinase concentration where no cause has been identified after neurological study (idiopathic hyperCKemia).
- Heat stroke by effort that requires hospital admission, where known predisposing factors have been excluded.
- Other myopaties Extreme physical activity, as well as environments with high temperatures favor the appearance of ischemia, anoxia and release of calcium from the sarcoplasmic reticulum, thus increasing the risk of developing MH.
There are also other infrequent diseases in which there is a ryanodine canalopathy by a mechanism similar to that seen in MH, but in cells of tissues other than skeletal striated muscle; as well as some drugs and other rare diseases that may be related to MH.
Despite the rarity of MH and given the severity of the disease clinic, it is mandatory to explore possible risks in patients with hypermetabolic response of skeletal musculature due to rare or trigger diseases (medications, drugs of abuse, exercise, extreme heat, others) whose MH risk is not defined.
Although the standard method for the diagnosis of MH is the in vitro test for halothane caffeine contraction (IVCT), it has been described that B lymphocytes of patients with MH have metabolic alterations. Alto, there are about 50 genetic variants associated with MH that have been described.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Population in risk of MH | – | Diagnostic Test: In vitro contracture test (IVCT), Diagnostic Test: In vitro test of hypermetabolism in B lymphocytes, Diagnostic Test: Genetic testPatient with hypermetabolic response of skeletal musculature by causes related with Malignant Hyperthermia in the literature. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patient with hypermetabolic response of skeletal musculature by related causes in the literature with Malignant Hyperthermia.
Key inclusion criteria (2 listed)
- Patients who have suffered at least one episode of rhabdomyolysis due to related causes in the literature with susceptibility to HM.
- Patients who have been given information about the study and have agreed to sign the consent of the study. The muscle biopsy will be performed under usual clinical practice.
Key exclusion criteria (2 listed)
- Patients who have suffered episodes of rhabdomyolysis due to alternative causes: trauma, compression hypoxia during immobilization or loss of consciousness or infectious arterial occlusion (influenza A and B, coxackievirus, Epstein-Barr, HIV, legionella, Streptococcus pyogenes Staphilococcus aureus, clostridium), metabolic or electrolyte abnormalities (hypokalemia, hypophosphatemia, hypocalcemia, non-ketosic hyperosmolar conditions, diabetic ketoacidosis), others.
- Children under 10 years or less than 30 kg are excluded for the in vitro test (muscle biopsy).
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 |
|---|---|---|
| In vitro contracture test (IVCT)In vitro study of muscle contraction after exposure to different substances (caffeine and halothane). | Diagnostic test | Population in risk of MH |
| In vitro test of hypermetabolism in B lymphocytesIn vitro study of the activation of lymphocytes B after being incubated with a cocktail of primary antibodies and measuring the acidification in response to the RyR1, 4-CmC agonist, using ryanodine as a positive control. | Diagnostic test | Population in risk of MH |
| Genetic testAnalysis of genes related to MH (CACNA1S and RYR1). | Diagnostic test | Population in risk of MH |
Primary outcome
Determination, by an in vitro study of muscular contraction, measuring the muscle tension, of the presence of Malignant Hyperthermia susceptibility in patients with a history of hypermetabolic response of skeletal musculature.
Time frame: 5 years
Measured by the tension induced by the muscular contraction in response to the presence of caffeine and halothane.
Determination, by genetic study, of the presence of susceptibility to Malignant Hyperthermia in patients with a history of hypermetabolic response of skeletal musculature.
Time frame: 5 years
Identifying determined genes related with Malignant Hyperthermia risk.
Study of the concordance of the genetic study and IVCT versus the hypermetabolic response of B lymphocyte, in patients with a history of hypermetabolic response of skeletal musculature.
Time frame: 5 years
Extracellular acidification curve in B lymphocytes in response to the agonist RyR1 and 4-CmC.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2022.
Related trials for Hyperthermia, Malignant
Active, not recruitingPhase 2
Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Pancreatic Cancer and Peritoneal Metastasis
Metastatic Pancreatic Carcinoma, Stage IV Pancreatic Cancer AJCC v8
RecruitingPhase 2
A Study of Additional Chemotherapy After Surgery for People With Malignant Peritoneal Mesothelioma
Malignant Peritoneal Mesothelioma, Peritoneal Mesothelioma
Enrolling by invitationObservational study
Study on the Efficacy and Safety of Different Doses of PEG-rhG-CSF for Primary Prevention of Febrile Neutropenia
Malignant Tumor
RecruitingPhase 2
Phase II Study of QLC2519 in Pediatric Solid Tumor Participants
Pediatric Malignant Solid Tumor, Febrile Neutropenia (FN)
Recruiting
Telehealth Intervention for Improving Distress and Financial Toxicity in the Caregivers
Hematopoietic and Lymphatic System Neoplasm, Malignant Solid Neoplasm
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.
Elena Ramírez García principal investigator
Clinical Pharmacology Department, La Paz University Hospital
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 Hyperthermia, Malignant, run by Instituto de Investigación Hospital Universitario La Paz at 1 site in Spain.
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 2 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 13 Jan 2022. 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 Spain. 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?
Contact Elena Ramírez García (+34 917277559, elena.ramirezg@uam.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination, by an in vitro study of muscular contraction, measuring the muscle tension, of the presence of Malignant Hyperthermia susceptibility in patients with a history of hypermetabolic response of skeletal musculature. (time frame: 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jan 2022.