Malignant HyperthermiaNCT02964481
Malignant Hyperthermia Registry and Genetic Testing
An observational study of Malignant Hyperthermia, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Malignant Hyperthermia
- What is being tested?
- Whole exome sequencing
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Aug 2015to 28 Feb 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients with documented MH clinical presentation and CHCT negative controls from NAMHR
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: Donation of Blood for Genetic Testing With Clinical Data From the North American Malignant Hyperthermia Registry
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.
Read the 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.
- Conditions
- Malignant Hyperthermia
- Being tested
- Whole exome sequencing
- Keywords
- malignant, genetics, RYR1, CAC-NA1S, hyperthermia
- Medical subject headings
- Malignant Hyperthermia, Hyperthermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Whole exome sequencingGenetic
DNA sequencing of protein coding sections of all genes
| Study group | Role | What they receive |
|---|---|---|
| Malignant Hyperthermia Phenotype cases | Samples from persons who identify as having the malignant hyperthermia phenotype by the North American MH Registry (NAMHR) Receives: 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) Receives: Genetic: Whole exome sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Within data collection period (5 years total).
Secondary outcomes (2)
Genomic factors that influence Malignant Hyperthermia.
A Batesian inference algorithm based on multiple genetic risk factors assessed from DNA data collected
Measured: Within data collection period (5 years total).
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
Measured: Indefinite - dependent on funding
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2016 (estimated)
- Study start18 Aug 2015
- Primary completion28 Feb 2017
- Study completion28 Feb 2017
Why it stopped: Lack of funding to enroll additional participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant HyperthermiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02964481
- Sponsor's protocol ID
- 2015-1749
- Status last verified
- Aug 2020
- First submitted
- 29 Jun 2016
- Last updated
- 3 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 31559918
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donation of Blood for Genetic Testing With Clinical Data From the North American Malignant Hyperthermia Registry
- ClinicalTrials.gov ID
- NCT02964481
- Acronym / sponsor ID
- 2015-1749
- Conditions
- Malignant Hyperthermia
- Keywords
- malignant, genetics, RYR1, CAC-NA1S, hyperthermia
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Lack of funding to enroll additional participants
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- 18 Aug 2015 (actual)
- Primary completion
- 28 Feb 2017 (actual)
- Study completion
- 28 Feb 2017 (actual)
- First posted
- 16 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Malignant Hyperthermia Phenotype cases | – | Genetic: Whole exome sequencingSamples from persons who identify as having the malignant hyperthermia phenotype by the North American MH Registry (NAMHR) |
| Caffeine Halothane Contracture Test negative controls | – | Genetic: Whole exome sequencingControls who had negative Caffeine Halothane Contracture Test (CHCT) from North American MH Registry (NAMHR) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with documented MH clinical presentation and CHCT negative controls from NAMHR
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Whole exome sequencingDNA sequencing of protein coding sections of all genes | Genetic | Caffeine Halothane Contracture Test negative controls, Malignant Hyperthermia Phenotype cases |
Primary outcome
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
2 secondary outcomes
Genomic factors that influence Malignant Hyperthermia.
Time frame: Within data collection period (5 years total).
Induced pluripotent stem cells will be used for functional testing and gene editing
Time frame: Indefinite - dependent on funding
Results and safety
The study was stopped early (reason given: Lack of funding to enroll additional participants). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2020.
- Results publication: PubMed 31559918Sadhasivam 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malignant Hyperthermia, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Lack of funding to enroll additional participants). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genetic comparison of MH phenotype subjects to that of the CHCT negative control subjects. (time frame: Within data collection period (5 years total).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02964481, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2020.