Rolandic Epilepsy Genomewide Association International Study (REGAIN)

We have discovered a small change in the genetic code which increases the risk of the brainwave abnormality that is found in rolandic epilepsy. We now wish to confirm this using a second much larger sample of patients. We will investigate the other genetic changes that cause people with the brainwave abnormality to develop seizures, as well as problems with speech, coordination, attention and learning.

Study Overview

• Status: Completed
• Conditions: Rolandic Epilepsy
• Intervention / Treatment: Other: Blood draw; Other: Existing samples

Detailed Description

Epilepsy is a common neurological disorder affecting 1% of the population. There are over 30 types of epilepsy, some common, some rare. Most epilepsies arise in childhood and have a genetic cause. Approximately 25% of child patients have "Rolandic Epilepsy" or RE, also known as Benign Epilepsy with Centrotemporal Spikes (BECTS). RE has a complex genetic basis, probably made up of combinations of susceptibility variants in different genes. Children with RE quite often have other symptoms that affect their speech, attention, reading ability or coordination. The goal of this study is to find the genetic basis for susceptibility to seizures and associated comorbidities for RE using genomewide association approaches.

We know that RE has a genetic basis and we recently discovered the genetic cause of the EEG pattern seen in RE. The goal of REGAIN is to now find the genetic basis for susceptibility to seizures and the associated symptoms above. Our hope is to be able to improve diagnosis and understand why each child with RE is different, and perhaps point us towards new treatments that are more effective and have fewer side effects.

We will compare the genetic code of 3,000 children with RE against a similar number of people not affected by epilepsy. With the proposed large sample of participants, we will be able to pinpoint the exact changes that might lead to seizures or attention problems for example. Learning the genetic basis for these problems will deepen our understanding of the mechanisms and lead to new treatments or cures.

• Study Type: Observational
• Enrollment (Actual): 210

Contacts and Locations

• Study Contact: Name: Professor Deb K Pal, MA MSc PhD MRCP; Phone Number: +44 (020) 7848 5162; Email: amber.collingwood@kcl.ac.uk
• Study Contact Backup: Name: Amber Collingwood, MA

Study Locations

• Argentina
  • Buenos Aires, Argentina, C 1245
    • Dr. Juan P. Garrahan Children's Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 0A4
      • Hospital for Sick Kids
• Greece
  • Athens, Greece, 115 27
    • Aghia Sophia Children's Hospital of Athens
• Italy
  • Catania, Italy, 95124
    • Sicilian Epilepsy Network
  • Roma, Italy, 00198
    • Commissione Genetica Lega Italiana contro l'Epilepssia
• Spain
  • Barcelona, Spain, 08221
    • Hospital Mutua De Terrassa
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XN
    • Cardiff University School of Medicine
  • London, United Kingdom, SE1 9HT
    • Guy's and St Thomas' NHS Foundation Trust
  • London, United Kingdom, SE5 8RX
    • King's College Hospital NHS Foundation Trust
  • Swansea, United Kingdom, SA2 8PP
    • Swansea University College of Medicine
• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Hasbro Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 23 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Target population is 3,000 participants with a diagnosis of Rolandic Epilepsy (1,000 UK).

Description

Inclusion Criteria:

1. Diagnosis of Rolandic Epilepsy in accordance with the following international criteria:

   • Age of first afebrile seizure 3-12 years
   • Seizures comprising focal sensorimotor seizures affecting the vocal tract and face, with or without involvement of the arm
   • Predominant sleep-related seizures
   • EEG interictal centro-temporal spikes with normal background
2. Current age 6-25 years

Exclusion Criteria:

1. No history of focal seizure
2. Normal EEG or abnormal background features on EEG
3. Known structural causes (stroke, tuberous sclerosis, infection, post-infectious or metabolic)
4. Primary diagnosis of autism or global learning disability
5. Focal central neurological deficit on clinical exam,
6. Unable to provide informed consent
7. Unable to provide blood sample

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Controls; People without a lifetime history of seizures.	Other: Existing samples; Control DNA samples will be used that have been previously acquired in other studies.
Patients diagnosed with RE; People who meet the eligibility requirements and have been diagnosed with rolandic epilepsy.	Other: Blood draw; Participation includes one visit for one blood draw per recruited patient. 10-20ml peripheral venous blood will be taken from the antecubital fossa. The DNA from the blood sample will then be extracted and resequenced for analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Allelic association p value corrected for genome wide testing	We will look to see if there are changes in the genetic code that cause brainwave abnormalities close to the genetic changes that we have already discovered.	Day 1

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: King's College Hospital NHS Trust; The Hospital for Sick Children; Cardiff University; Columbia University; Seattle Children's Hospital; Guy's and St Thomas' NHS Foundation Trust; Hasbro Children's Hospital; Hospital Mutua de Terrassa; Aghia Sophia Children's Hospital of Athens; Hospital JP Garrahan

Publications and helpful links

Helpful Links

• Childhood Epilepsy website

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): March 17, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Epilepsy; Genomewide Association Study; Genetics; Pediatrics; Neurology; Rolandic; RE
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Epilepsies, Partial; Epilepsy; Epilepsy, Rolandic
• Other Study ID Numbers: 229844; TWF 164-3020 (Other Grant/Funding Number: The Waterloo Foundation)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No