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Malignant Hyperthermia Registry and Genetic Testing

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02964481
Recruitment Status : Terminated (Lack of funding to enroll additional participants)
First Posted : November 16, 2016
Last Update Posted : September 3, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Malignant Hyperthermia Genetic: Whole exome sequencing

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.

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Study Type : Observational
Actual Enrollment : 64 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Donation of Blood for Genetic Testing With Clinical Data From the North American Malignant Hyperthermia Registry
Actual Study Start Date : August 18, 2015
Actual Primary Completion Date : February 28, 2017
Actual Study Completion Date : February 28, 2017

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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
DNA sequencing of protein coding sections of all genes

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
DNA sequencing of protein coding sections of all genes




Primary Outcome Measures :
  1. Genetic comparison of MH phenotype subjects to that of the CHCT negative control subjects. [ Time Frame: 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 :
  1. Genomic factors that influence Malignant Hyperthermia. [ Time Frame: Within data collection period (5 years total). ]
    A Batesian inference algorithm based on multiple genetic risk factors assessed from DNA data collected

  2. Induced pluripotent stem cells will be used for functional testing and gene editing [ Time Frame: Indefinite - dependent on funding ]
    Induced pluripotent stem cells will be made for future in-vitro analysis


Biospecimen Retention:   Samples With DNA
Blood samples will be used to extract DNA for genotyping, pyrosequencing and pluripotent stem cells.


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients with documented MH clinical presentation and CHCT negative controls from NAMHR
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02964481


Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Publications of Results:
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02964481    
Other Study ID Numbers: 2015-1749
First Posted: November 16, 2016    Key Record Dates
Last Update Posted: September 3, 2020
Last Verified: August 2020
Keywords provided by Children's Hospital Medical Center, Cincinnati:
malignant
genetics
RYR1
CAC-NA1S
hyperthermia
Additional relevant MeSH terms:
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Fever
Malignant Hyperthermia
Body Temperature Changes
Intraoperative Complications
Pathologic Processes
Postoperative Complications