Malignant Hyperthermia Registry and Genetic Testing

Terminated

• Conditions: Malignant Hyperthermia
• Interventions: Genetic: Whole exome sequencing

• Registration Number: NCT02964481
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

The purpose of this study is to to determine the penetrance of known and probable pathogenic variants in genes and the factors that contribute to penetrance in a population of children and adults in the United States exposed to Malignant Hyperthermia (MH) trigger agents.

Detailed Description

The purpose of the study is to determine how genetic mutations and variants in combination with non-genetic factors influence risk for MH in children who had general anesthesia with triggering agents and develop reliable predictive MH risk algorithms. Rationale: Once the factors responsible for MH risk are determined, it will be possible to better predict risk and develop better individualization of anesthetics such as tailored selection of intravenous anesthetics, regional anesthesia and avoidance of all triggering agents. The long-term goal is to tailor and improve safety of anesthetic and clinical care and to reduce mortality, morbidity and cost of care due to MH with right anesthetics and muscle relaxants for endotracheal intubations for an individual child.

Study Timeline

• Study Start: 2015-08-18
• Study First Submitted: 2016-06-29
• Study First Submitted QC: 2016-11-11
• Study First Posted: 2016-11-16
• Primary Completion: 2017-02-28
• Study Completion: 2017-02-28
• Status Verified: 2020-08
• Last Update Submitted: 2020-09-01
• Last Update Posted: 2020-09-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

• Any English speaking person registered at NAHMR who has had a positive clinical manifestation of Malignant Hyperthermia
• Any person with a positive Caffeine Halothane Contracture probTest (CHCT) or a close relative of a person that had these.

Exclusion Criteria

• Any person who has NOT had a positive clinical manifestation of Malignant Hyperthermia
• Any person with a positive Caffeine Halothane Contracture Test (CHCT) or NOT a close relative of a person that had these. Non-English speaking registrants will be excluded.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Malignant Hyperthermia Phenotype cases	Whole exome sequencing	Samples from persons who identify as having the malignant hyperthermia phenotype by the North American MH Registry (NAMHR)
Caffeine Halothane Contracture Test negative controls	Whole exome sequencing	Controls who had negative Caffeine Halothane Contracture Test (CHCT) from North American MH Registry (NAMHR)

Primary Outcome Measures

Name	Time	Method
Genetic comparison of MH phenotype subjects to that of the CHCT negative control subjects.	Within data collection period (5 years total).	MHS subjects and CHCT negative controls recruited from the North American MH Registry will have whole genome sequencing

Secondary Outcome Measures

Name	Time	Method
Genomic factors that influence Malignant Hyperthermia.	Within data collection period (5 years total).	A Batesian inference algorithm based on multiple genetic risk factors assessed from DNA data collected
Induced pluripotent stem cells will be used for functional testing and gene editing	Indefinite - dependent on funding	Induced pluripotent stem cells will be made for future in-vitro analysis

Trial Locations

Locations (1)

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States