A Pharmacogenomic Exploration of Lacosamide Response

This is an observational study exploring the genetics of lacosamide response. The study will last 3 years and has been divided in to three stages; 1) recruitment, 2) observational phase, 3) genotyping and analysis. Patients initiating lacosamide are recruited and their baseline seizure frequency is assessed retrospectively. Patients are then monitored for 18 months with an assessment (via interview and where possible seizure diaries) of seizure frequency and other treatment related phenotypes every 3 months. The recruitment period will span months 1-12, the observational period will span months 1-30 and analysis of data will be conducted between months 30-36 (see Figure 2 below). Target sample size is 610.

Primary objective: To determine the clinical relevance of genetic variation in predicting lacosamide responsive and non-responsive patients.

Secondary objectives: To determine the clinical relevance of genetic variation in predicting:

• Optimal dose of lacosamide
• Adverse drug reactions to lacosamide

Study Overview

• Status: Unknown
• Conditions: Epilepsy

• Study Type: Observational
• Enrollment (Anticipated): 660

Contacts and Locations

• Study Contact: Name: Gianpiero Cavalleri, PhD; Phone Number: +353 1 4022146; Email: gcavalleri@rcsi.ie

Study Locations

• Belgium
  • Brussels, Belgium
    • Recruiting
    • Hospital Erasme
    • Contact: Chantal Depondt
• Ireland
  • Dublin, Ireland, D4
    • Recruiting
    • Beaumont Hospital
    • Contact: Gianpiero Cavalleri, PhD; Phone Number: +353 1 4022146; Email: gcavalleri@rcsi.ie
    • Principal Investigator: Norman Delanty
  • Dublin, Ireland
    • Recruiting
    • St.James Hospital
    • Contact: Colin Doherty
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • The Institute of Neurology
    • Contact: Sanjay Sisodiya
• United States
  • North Carolina
    • Durham, North Carolina, United States
      • Recruiting
      • Duke Medical Centre
      • Contact: Saraubh Sinha

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with epilepsy recruited from five tertiary referral centres.

Description

Inclusion Criteria:

• Diagnosed with partial onset seizures (simple and/or complex) with or without secondary generalization (based on 1981 ILAE seizure classification scheme)
• Over 18 and under 65 years of age at date of recruitment in to the study
• Currently undergoing pharmacological treatment for refractory partial epilepsy ('refractory' here refers to patients who continue to have seizures despite treatment (current) with two or more appropriate anti-epileptic drugs at appropriate doses)
• Deemed suitable for treatment with lacosamide (following drug guidelines)

Exclusion Criteria:

• Patients experiencing seizure type other than partial onset seizures (with/without secondary generalisation)
• Patients with a history of chronic alcohol or drug abuse within previous 3 years.
• Non refractory epilepsy patients
• Patients suffering any other clinically significant disease e.g. cancers, progressive neurological disorder, heart failure, respiratory failure etc
• Patients who are pregnant or who are intending on getting pregnant within the period of the trial.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Beaumont Hospital, Dublin, Ireland
St. James' Hospital, Dublin, Ireland
Hôpital Erasme, Brussels, Belgium
Duke Medical Centre, North Carolina, USA
The Institute of Neurology/University College London, UK

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizure frequency	We will record seizure type and frequency. Seizure types will follow definitions as provided by the International League Against Epilepsy. Seizure frequency will be as recorded by the participant in a seizure diary.	Recorded daily by participant. Passed on to study researchers every 3 months for an 18 month period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance dose	Maintenance dose will be defined as the tolerated daily dose required by the patient for seizure control.	Recorded every three months for an 18 month period
Adverse drug reactions	We will record any adverse reactions recorded by the study participant, including for example (but not limited to): dizziness, ataxia, vomiting, diplopia, nausea, vertigo, and vision blurred.	Recorded as reaction arise during the 18 month study period

Collaborators and Investigators

• Sponsor: Royal College of Surgeons, Ireland
• Collaborators: Duke University; University College, London; St. James's Hospital, Ireland; Erasme University Hospital
• Investigators: Principal Investigator: Norman Delanty, MB FRCPI, Beaumont Hospital and Royal College of Surgeons in Ireland; Principal Investigator: Gianpiero L Cavalleri, PhD, Royal College of Surgeons in Ireland

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): March 1, 2014
• Study Completion (Anticipated): March 1, 2014

Study Registration Dates

• First Submitted: July 20, 2011
• First Submitted That Met QC Criteria: July 20, 2011
• First Posted (Estimate): July 21, 2011

Study Record Updates

• Last Update Posted (Estimate): December 7, 2012
• Last Update Submitted That Met QC Criteria: December 5, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: RCSI_LCM