Clinical trial NCT02964481: Malignant Hyperthermia Registry and Genetic Testing
Official title: Donation of Blood for Genetic Testing With Clinical Data From the North American Malignant Hyperthermia Registry
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Malignant Hyperthermia
Keywords: malignant
genetics
RYR1
CAC-NA1S
hyperthermia
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2016-11-16
Enrollment: 64
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with documented MH clinical presentation and CHCT negative controls from NAMHR

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Genetic comparison of MH phenotype subjects to that of the CHCT negative control subjects.
timeFrame: Within data collection period (5 years total).
Secondary outcomes:
measure: Genomic factors that influence Malignant Hyperthermia.
timeFrame: Within data collection period (5 years total).
measure: Induced pluripotent stem cells will be used for functional testing and gene editing
timeFrame: Indefinite - dependent on funding
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
References:
citation: 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.