Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients

Study Overview
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Brief Summary
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This is a post-market medical device study. This study will compare best medical practice with or without adjunctive VNS Therapy in patients who are 16 years and older with pharmacoresistant partial epilepsy.

Detailed Description
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This is a post-market medical device study. This study will compare best medical practice with or without adjunctive VNS Therapy in patients who are 16 years and older with pharmaco-resistant partial epilepsy. The Sponsor, Cyberonics, provides funding for this study. Patients are followed for 26 months, 24 of those months are following the initiation of treatment. No study sites will be permitted to enroll study subjects until Institutional Review Board (IRB)/Ethics Committee (EC) approval has been received.

Official Title
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An Open Prospective Randomised Long-Term Effectiveness Study, Comparing Best Medical Practice With or Without Adjunctive VNS Therapy in Patients 16 Years and Older With Pharmaco-resistant Partial Epilepsy

Conditions
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Epilepsy, Partial Epilepsy

Intervention / Treatment
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* Device: Vagal Nerve Simulation (VNS) Therapy
* Drug: Best Medical Practive


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has confirmed partial onset seizures. Seizure activity is not adequately controlled by patient's current AED regimen. Patient is between 16 and 75 years of age. Patient is able to give accurate seizure counts and health outcomes information. Patient is able to complete study instruments with minimal assistance. Patient has previously failed at least 3 AEDs in single or combination use. During baseline evaluation period, patient should take at least 1 AED. Patient should have confirmed epilepsy for a minimum of 2 years. Patient's AED regimen is stable for at least 1 month prior to enrolment. Patient has at least 1 objective partial onset seizure per month during the 2 months prior to enrolment. Patient or legal guardian understands study procedures and has voluntarily signed an informed consent in accordance with institutional and local regulatory policies. Exclusion Criteria: Patient has pseudoseizures or a history of pseudoseizures. Patient has idiopathic generalised epilepsy or unclassified epilepsy. Patient has ever received direct brain stimulation (cerebella or thalamic) for treatment of epilepsy. Patient has had a unilateral or bilateral cervical vagotomy. Patient has a history of non-compliance with the completion of a seizure diary. Patient has taken an investigational drug within a period of 3 months prior to inclusion. Patient is currently using another investigational medical device. Patient has a significant cardiac or pulmonary condition currently under treatment. Patient has previously undergone brain surgery. Patient has a demand cardiac pacemaker, implantable defibrillator, or other implantable stimulator. Patient currently lives more than 2 hours from the study site or plans to relocate to a location more than 2 hours from the study site within one year of enrolment in the Study.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VNS Therapy<br>VNS Therapy + Best Medical Practice | Device: Vagal Nerve Simulation (VNS) Therapy<br>* VNS Therapy + Best Medical Practice including anti-epileptic drugs<br>|
| Active Comparator: Best Medical Practice<br>Best Medical Practice | Drug: Best Medical Practive<br>* Best Medical Practice including anti-Epileptic Drugs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Quality of Life in Epilepsy-89 (QOLIE-89) Score in Patients With Baseline & at Least One Post-baseline QOLIE Assessment | QOLIE-89 contains 17 multi-item measures of overall quality of life, emotional well-being, role limitations due to emotional problems, social support, social isolation, energy/fatigue, worry about seizure, medication effects, health discouragement, work/driving/social function, attention/concentration, language, memory, physical function, pain, role limitations due to physical problems, and health perceptions. Range of values 0-100. Higher scores reflect better quality of life; lower ones, worse quality of life. | Mean change from baseline QOLIE-89 Overall Score at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Response Rate is defined as the percent of participants who are responders. A Responder is defined as participants with a reduction of at least 50% or 75% in seizure frequency from baseline to the seizure count evaluation period. | Number of Responders at 12 Months | 
| Percent of Patients That Are Seizure Free | Percent of patients that are seizure free as defined by no seizures during the preceding follow-up period. | 3, 6, 9, 12, 15, 18, 21, 24 months | 
| Mean Percent Change in Seizure Frequency | Percent change in total seizuires per week from baseline at 12 months | Mean percent change from baseline in seizure frequency at 12 months | 
| Seizure Free Days | Seizure free days is defined as the time from last seizure to study exit date. | From the patient's last seizure to the study exit date | 
| Seizure Free Days Over the Last 6 Months |  | Over the last 6 months | 
| Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Score | The Center for Epidemiologic Studies Depression Scale (CES-D) includes 20 items comprising six scales reflecting major dimensions of depression: depressed mood, feelings of guilt and worthlessness, feelings of helplessness and hopelessness, psychomotor retardation, loss of appetite, and sleep disturbance. Possible range of scores is 0 to 60, higher scores indicate more depressive symptoms. | Mean change from baseline CES-D Score at 12 months | 
| Change From Baseline in Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score | The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a 6-item questionnaire validated to screen for depression in people with epilepsy. Scores range from 6 to 24, with higher scores indicating more depressive symptoms. | Mean change from baseline NDDI-E Score at 12 months | 
| Mean Change From Beginning of Intervention Clinical Global Impression-Improvement Scale (CGI-I) Score at 12 Months | The Clinical Global Impression scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention Scores range from 1-7: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. | Mean change from baseline CGI-I Score at 12 months | 
| Change From Baseline in Adverse Event Profile (AEP) Score | Adverse Events Profile (AEP) is a 19-item scale used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). Scores range from 19-76; higher scores indicate high prevelance and severity of adverse events. | Mean change from baseline AEP Score at 12 months | 
| Changes in Anti-epileptic Drugs (AEDs) | Change from baseline in number of AED medications by visit | Change from baseline in number of AEDs at 12 months | 
| Retention Rate | Percent of participants who were compliant with the protocol. | At 12 and 24 months | 
| Treatment Emergent Adverse Events, Device Complications, and Premature Study Withdrawal | Number of participants with treatment emergent adverse events, device complications, and premature Study withdrawal. | At 12 and 24 months | 
| Quality of Life in Epilepsy - 89 Items(QOLIE-89)in Patients With Less Than a 50% Reduction in Seizures | QOLIE-89 contains 17 multi-item measures of overall quality of life, emotional well-being, role limitations due to emotional problems, social support, social isolation, energy/fatigue, worry about seizure, medication effects, health discouragement, work/driving/social function, attention/concentration, language, memory, physical function, pain, role limitations due to physical problems, and health perceptions. Range of values 0-100. Higher scores reflect better quality of life; lower ones, worse quality of life. | At 12 and 24 months | 
| Centre for Epidemiologic Studies Depression Scale (CES-D) in Patients With Less Then a 50% Reduction | The Center for Epidemiologic Studies Depression Scale (CES-D) includes 20 items comprising six scales reflecting major dimensions of depression: depressed mood, feelings of guilt and worthlessness, feelings of helplessness and hopelessness, psychomotor retardation, loss of appetite, and sleep disturbance. Possible range of scores is 0 to 60, higher scores indicate more depressive symptoms. | At 12 and 24 months | 
| Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) in Patients With Less Then a 50% Reduction in Seizures | The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a 6-item questionnaire validated to screen for depression in people with epilepsy. Scores range from 6 to 24, with higher scores indicating more depressive symptoms. | At 12 and 24 months | 
| Adverse Event Profile (AEP) in Patients With Less Then a 50% Reduction in Seizures | Adverse Events Profile (AEP) is a 19-item scale used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). Scores range from 19-76; higher scores indicate high prevelance and severity of adverse events. | At 12 and 24 months | 
| Change in the Number of Anti-epileptic Drugs Prescribed | Changes in Anti-Epileptic Drugs (AEDs) in patients with less then a 50% reduction in seizures | At 12 and 24 months | 
| Percent of Participants Who Were Compliant With the Protocol | Retention rate in patients with less then a 50% reduction in seizures | At 12 and 24 months | 
| Change From Baseline in QOLIE-89 Measures: Subgroup Analysis of Population With Baseline Adverse Event Profile Score >= 40 | QOLIE-89 contains 17 multi-item measures of overall quality of life. Range of values 0-100. Higher scores reflect better quality of life; lower ones, worse quality of life. Adverse Events Profile (AEP) is a 19-item scale used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). Scores range from 19-76; higher scores indicate high prevelance and severity of adverse events. | Change from baseline up to 12 months | 
| Change From Baseline in QOLIE-89 Measures: Subgroup Analysis of Population With Baseline Adverse Event Profile Score < 40 | QOLIE-89 contains 17 multi-item measures of overall quality of life. Range of values 0-100. Higher scores reflect better quality of life; lower ones, worse quality of life. Adverse Events Profile (AEP) is a 19-item scale used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). Scores range from 19-76; higher scores indicate high prevelance and severity of adverse events. | Change from baseline up to 12 months | 
| Clinical Global Impressions Scale (CGI) in Patients With Less Then a 50% Reduction in Seizures | The Clinical Global Impression scale (CGI-I)is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention Scores range from 1-7: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. | At 12 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, VNS Therapy