Population at Risk of Malignant Hyperthermia: Ambispective Cohort.

NCT04287556 | Unknown

• 1 other identifier: HUL-RHM-2019
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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 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).

Conditions

Hyperthermia, Malignant

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  5 years

Study Arms (1)

Population in risk of MH

Patient with hypermetabolic response of skeletal musculature by causes related with Malignant Hyperthermia in the literature.

Diagnostic Test: In vitro contracture test (IVCT); Diagnostic Test: In vitro test of hypermetabolism in B lymphocytes; Diagnostic Test: Genetic test

Interventions

In vitro contracture test (IVCT) DIAGNOSTIC_TEST

In vitro study of muscle contraction after exposure to different substances (caffeine and halothane).

Population in risk of MH

In vitro test of hypermetabolism in B lymphocytes DIAGNOSTIC_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.

Population in risk of MH

Genetic test DIAGNOSTIC_TEST

Analysis of genes related to MH (CACNA1S and RYR1).

Population in risk of MH

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patient with hypermetabolic response of skeletal musculature by related causes in the literature with Malignant Hyperthermia.

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Instituto de Investigación Hospital Universitario La Paz: lead
• Universidad Autonoma de Madrid: collaborator

Study Sites (1)

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

50 variants have been described that can be considered "diagnostic mutations" of RYR1 and CACNA1S, and other under study.

MeSH Terms

Conditions

Malignant Hyperthermia

Interventions

Genetic Testing

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Elena Ramírez García

  Clinical Pharmacology Department, La Paz University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elena Ramírez García

CONTACT

+34 917277559; elena.ramirezg@uam.es

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: February 27, 2020
• Study Start: February 26, 2020
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: January 13, 2022

Record last verified: 2021-08

Locations

ES (1)