Malignant Hyperthermia Registry and Genetic Testing

NCT02964481 | Terminated

• 1 other identifier: 2015-1749
• Study Type: observational
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Malignant Hyperthermia

Keywords

malignant; genetics; RYR1; CAC-NA1S; hyperthermia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Genomic factors that influence Malignant Hyperthermia.

  Within data collection period (5 years total).

• Induced pluripotent stem cells will be used for functional testing and gene editing

  Indefinite - dependent on funding

Study Arms (2)

Malignant Hyperthermia Phenotype cases

Samples from persons who identify as having the malignant hyperthermia phenotype by the North American MH Registry (NAMHR)

Genetic: Whole exome sequencing

Caffeine Halothane Contracture Test negative controls

Controls who had negative Caffeine Halothane Contracture Test (CHCT) from North American MH Registry (NAMHR)

Genetic: Whole exome sequencing

Interventions

Whole exome sequencing GENETIC

DNA sequencing of protein coding sections of all genes

Caffeine Halothane Contracture Test negative controls; Malignant Hyperthermia Phenotype cases

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with documented MH clinical presentation and CHCT negative controls from NAMHR

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related 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.

  PMID: 31559918 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be used to extract DNA for genotyping, pyrosequencing and pluripotent stem cells.

MeSH Terms

Conditions

Malignant Hyperthermia; Hyperthermia

Interventions

Exome Sequencing

Condition Hierarchy (Ancestors)

Intraoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Body Temperature Changes; Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Whole Genome Sequencing; Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2016
• First Posted: November 16, 2016
• Study Start: August 18, 2015
• Primary Completion: February 28, 2017
• Study Completion: February 28, 2017
• Last Updated: September 3, 2020

Record last verified: 2020-08

Locations

US (1)