跳至主要内容
临床试验/NCT04287556
NCT04287556招募中不适用

Population at Risk of Malignant Hyperthermia: Ambispective Cohort.

Instituto de Investigación Hospital Universitario La Paz1 个研究点 分布在 1 个国家目标入组 90 人开始时间: 2020年2月26日最近更新:
适应症

试验速览

阶段
不适用
状态
招募中
入组人数
90
试验地点
1
主要终点
Determination, by genetic study, of the presence of susceptibility to Malignant Hyperthermia in patients with a history of hypermetabolic response of skeletal musculature.

研究概览

简要总结

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).

详细描述

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.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Other

入排标准

性别
All
接受健康志愿者

入选标准

  • 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.

排除标准

  • 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).

结局指标

主要结局

Determination, by genetic study, of the presence of susceptibility to Malignant Hyperthermia in patients with a history of hypermetabolic response of skeletal musculature.

时间窗: 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.

时间窗: 5 years

Extracellular acidification curve in B lymphocytes in response to the agonist RyR1 and 4-CmC.

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.

时间窗: 5 years

Measured by the tension induced by the muscular contraction in response to the presence of caffeine and halothane.

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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