Malignant Hyperthermia Registry and Genetic Testing

Malignant Hyperthermia Clinical Trial

Official title:

Donation of Blood for Genetic Testing With Clinical Data From the North American Malignant Hyperthermia Registry

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02964481
• Other study ID #: 2015-1749
• Status: Terminated
• Start date: August 18, 2015
• Est. completion date: February 28, 2017

Study information

• Verified date: August 2020
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 64
• Est. completion date: February 28, 2017
• Est. primary completion date: February 28, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Fever
• Malignant Hyperthermia

Intervention

Genetic:
• Whole exome sequencing
DNA sequencing of protein coding sections of all genes

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

References & Publications (1)

Sadhasivam S, Brandom BW, Henker RA, McAuliffe JJ. Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants. Pharmacogenomics. 2019 Sep;20(14):989-1003. doi: 10.2217/pgs-2019-0055. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genetic comparison of MH phenotype subjects to that of the CHCT negative control subjects.	MHS subjects and CHCT negative controls recruited from the North American MH Registry will have whole genome sequencing	Within data collection period (5 years total).
Secondary	Genomic factors that influence Malignant Hyperthermia.	A Batesian inference algorithm based on multiple genetic risk factors assessed from DNA data collected	Within data collection period (5 years total).
Secondary	Induced pluripotent stem cells will be used for functional testing and gene editing	Induced pluripotent stem cells will be made for future in-vitro analysis	Indefinite - dependent on funding