Genetic Markers of Cardiovascular Disease in Epilepsy

• ClinicalTrials.gov Identifier: NCT02824822
• Recruitment Status: Recruiting
• First Posted: July 7, 2016
• Last Update Posted: July 29, 2022
• Sponsor: Mayo Clinic
• Collaborator: American Heart Association
• Information provided by (Responsible Party): Virend Somers, MD, PhD, Mayo Clinic

Study Description

Brief Summary:

Epilepsy is a common condition which affects over 3 million people in the US. Patients with uncontrolled epilepsy have a lifetime risk of sudden unexpected death (SUDEP) of 35%, which is greatest in those under 40 years of age. The exact mechanisms and causes are not understood but can be due to underlying conditions which affect the heart and brain, which may lead to dangerous heart rhythms and death. Some of these conditions which affect heart and brain have an identifiable genetic cause. This study aims to identify known genetic causes of heart rhythm and sudden death related disorders in patients with epilepsy.

Condition or disease
Epilepsy; Seizures; Syncope; Channelopathy; Cardiomyopathies

Detailed Description:

The overall goals are to determine whether patients with epilepsy who have the highest risk of SUDEP have an underlying genetic cardiovascular disorder. The investigators are seeking patients with epilepsy who have a high risk of SUDEP identified by using a risk scoring tool called SUDEP-7 and/or have blood-relatives with a history of epilepsy, seizure, cardiac arrest, sudden death, drowning/near-drowning, syncope or heart rhythm disorder. The investigators may also include blood-relatives of patients with epilepsy and invite them to participate by providing a blood sample and/or buccal cells (from a swab or saliva) for genetic testing.

Study Design

• Study Type: Observational
• Estimated Enrollment: 600 participants
• Observational Model: Family-Based
• Time Perspective: Prospective
• Official Title: Genetic Markers of Cardiovascular Diseases and the Potential Role in Sudden Unexpected Death in Epilepsy.
• Study Start Date: May 2016
• Estimated Primary Completion Date: December 31, 2028
• Estimated Study Completion Date: December 31, 2029

Groups and Cohorts

Group/Cohort
High SUDEP risk cohort; Patients with epilepsy who have a high SUDEP-7 risk score and/or a blood-relative with epilepsy, seizure, cardiac arrest, sudden death, drowning/near-drowning, syncope or arrhythmia.
Low SUDEP risk cohort; Patients with epilepsy and a low SUDEP-7 score.

Outcome Measures

Primary Outcome Measures :

1. Using Next Generation Whole-Exome Sequencing, determine if an underlying genetic cardiac mutation is present in refractory epilepsy patients who are at highest risk of sudden death. [ Time Frame: 3-5 years ]

   SUDEP-7 is a risk profiling tool, with a score ranging from 0-12. Generally, a score greater than or equal to 3 is considered high risk. The investigators will select participants with a family history of epilepsy, seizures, cardiac arrest, sudden death, drowning, syncope or arrhythmia, as this markedly increases genetic yield.

   Next Generation Whole-Exome Sequencing will be performed with a focus on known genes implicated in sudden unexpected death syndromes (channelopathies, cardiomyopathies and aortopathies) and autonomic control. Where relevant, blood-relatives may be invited for genomic 'trio' analyses.

Biospecimen Retention:   Samples With DNA

50 mls of blood from a vein will be drawn at Mayo Clinic or another medical center and returned through the mail. Buccal swabs will be collected using a swab and saliva based-kit.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Men and women diagnosed with epilepsy or seizures or unexplained syncope and blood relatives.

Criteria

Inclusion Criteria:

• Adults ages 18 - 50 with a diagnosis of epilepsy or seizures, or syncope or drowning or cardiac arrest or sudden death or an abnormal ECG suggestive of an arrhythmia
• Blood-relatives (Aged 18+) of a patient with a history of epilepsy, seizure, cardiac arrest, sudden death, drowning, syncope or arrhythmia

Exclusion Criteria:

• Those who are unable to provide written consent.
• Prisoners (vulnerable population)
• Seizures secondary to ischemic events
• Traumatic brain injury resulting in seizures
• History of cranial surgery
• History of brain tumor

Contacts and Locations

Contacts

Contact: Somers CPL Lab; CPL@mayo.edu

Locations

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Sub-Investigator: Erik K St. Louis, MD

Sub-Investigator: Anwar A Chahal, MD MRCP

Sub-Investigator: Michael J Ackerman, MD PhD

Sub-Investigator: Peter A Brady, MD FRCP FHRS

Sponsors and Collaborators

Mayo Clinic

American Heart Association

Investigators

• Principal Investigator: Virend K. Somers, MD PhD; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Virend Somers, MD, PhD, PI, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02824822
• Other Study ID Numbers: 15-002420
• First Posted: July 7, 2016
• Last Update Posted: July 29, 2022
• Last Verified: July 2022

Keywords provided by Virend Somers, MD, PhD, Mayo Clinic:

Sudden Unexpected Death in Epilepsy; SUDEP; Sudden Cardiac Arrest; Sudden Cardiac Death; Sleep; Ion channel disease; Long QT syndrome; Brugada; Catecholaminergic Polymorphic Ventricular Tachycardia

Additional relevant MeSH terms:

Epilepsy; Seizures; Syncope; Sudden Unexpected Death in Epilepsy; Cardiovascular Diseases; Cardiomyopathies; Channelopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Heart Diseases; Neurologic Manifestations; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Pathologic Processes; Death, Sudden; Death