Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients - Full Text View

Purpose

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.

Condition	Intervention	Phase
Epilepsy Partial Epilepsy	Device: Vagal Nerve Simulation (VNS) Therapy Drug: Best Medical Practive	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: autosomal dominant partial epilepsy with auditory features pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Epilepsy Neurologic Diseases Seizures

U.S. FDA Resources

Further study details as provided by Cyberonics, Inc.:

Primary Outcome Measures:

Quality of Life in Epilepsy (QOLIE-89) [ Time Frame: Mean score at 21 and 24 months ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Response Rate [ Time Frame: 3, 6 , 9, 12, 15, 18, 21, and 24 months ] [ Designated as safety issue: No ]
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.
Percent of Patients That Are Seizure Free [ Time Frame: 3, 6, 9, 12, 15, 18, 21, 24 months ] [ Designated as safety issue: No ]
Percent of patients that are seizure free as defined by no seizures during the preceding follow-up period.
Mean Percent Change in Seizure Frequency [ Time Frame: 3, 6, 9, 12, 15, 18, 21, 24 months ] [ Designated as safety issue: No ]
Mean percent change in seizure frequency compared to baseline value.
Seizure Free Days [ Time Frame: From the patient's last seizure to the study exit date ] [ Designated as safety issue: No ]
Seizure free days is defined as the time from last seizure to study exit date.
Seizure Free Days Over the Last 6 Months [ Time Frame: Over the last 6 months ] [ Designated as safety issue: No ]
Center for Epidemiologic Studies Depression Scale (CES-D) [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
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.
Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
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.
Clinical Global Impressions Scale (CGI) [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
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.
Adverse Event Profile (AEP) [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: Yes ]
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.
Changes in Anti-epileptic Drugs (AEDs) [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
Change in the number of anti-epileptic drugs perscribed.
Retention Rate [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
Percent of participants who were compliant with the protocol.
Treatment Emergent Adverse Events, Device Complications, and Premature Study Withdrawal [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: Yes ]
Number of participants with treatment emergent adverse events, device complications, and premature Study withdrawal.
Quality of Life in Epilepsy - 89 Items(QOLIE-89)in Patients With Less Than a 50% Reduction in Seizures [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
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.
Centre for Epidemiologic Studies Depression Scale (CES-D) in Patients With Less Then a 50% Reduction [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
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.
Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) in Patients With Less Then a 50% Reduction in Seizures [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
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.
Adverse Event Profile (AEP) in Patients With Less Then a 50% Reduction in Seizures [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: Yes ]
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 in the Number of Anti-epileptic Drugs Prescribed [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
Changes in Anti-Epileptic Drugs (AEDs) in patients with less then a 50% reduction in seizures
Percent of Participants Who Were Compliant With the Protocol [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
Retention rate in patients with less then a 50% reduction in seizures
Quality of Life in Epilepsy-89 (QOLIE-89) in Patients With a Baseline AEP Score Less Than 40 Versus Those Patients With a Baseline AEP Score Greater Than or Equal to 40 [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
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.
Clinical Global Impressions Scale (CGI) in Patients With Less Then a 50% Reduction in Seizures [ Time Frame: At 12 and 24 months ] [ Designated as safety issue: No ]
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.

Enrollment:	122
Study Start Date:	February 2006
Study Completion Date:	July 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: VNS Therapy VNS Therapy + Best Medical Practice	Device: Vagal Nerve Simulation (VNS) Therapy VNS Therapy + Best Medical Practice including anti-epileptic drugs
Active Comparator: Best Medical Practice Best Medical Practice	Drug: Best Medical Practive Best Medical Practice including anti-Epileptic Drugs

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00522418

Show 48 Study Locations

Sponsors and Collaborators

Cyberonics, Inc.

Investigators

Principal Investigator:	Phillippe Ryvlin, MD	Hopital Neurologique, Lyon, France
Study Director:	Sophie Leyman, MD	Cyberonics Europe

More Information

Publications:

Gilliam F. Optimizing health outcomes in active epilepsy. Neurology. 2002 Apr 23;58(8 Suppl 5):S9-20. Review.

Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9.

Sillanpaa M, Jalava M, Kaleva O, Shinnar S. Long-term prognosis of seizures with onset in childhood. N Engl J Med. 1998 Jun 11;338(24):1715-22.

Mattson RH, Cramer JA, Collins JF, Smith DB, Delgado-Escueta AV, Browne TR, Williamson PD, Treiman DM, McNamara JO, McCutchen CB, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med. 1985 Jul 18;313(3):145-51.

Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. N Engl J Med. 1992 Sep 10;327(11):765-71.

Mattson RH, Cramer JA, Collins JF. Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures. Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group. Neurology. 1996 Jul;47(1):68-76.

Schmidt D. The clinical impact of new antiepileptic drugs after a decade of use in epilepsy. Epilepsy Res. 2002 Jun;50(1-2):21-32. Review.

Lhatoo SD, Wong IC, Polizzi G, Sander JW. Long-term retention rates of lamotrigine, gabapentin, and topiramate in chronic epilepsy. Epilepsia. 2000 Dec;41(12):1592-6.

Morris GL 3rd, Mueller WM. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05. Neurology. 1999 Nov 10;53(8):1731-5. Erratum in: Neurology 2000 Apr 25;54(8):1712.

Malow BA, Edwards J, Marzec M, Sagher O, Ross D, Fromes G. Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients. Neurology. 2001 Sep 11;57(5):879-84.

Harden CL, Pulver MC, Ravdin LD, Nikolov B, Halper JP, Labar DR. A Pilot Study of Mood in Epilepsy Patients Treated with Vagus Nerve Stimulation. Epilepsy Behav. 2000 Apr;1(2):93-99.

Elger G, Hoppe C, Falkai P, Rush AJ, Elger CE. Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Res. 2000 Dec;42(2-3):203-10.

Clark KB, Naritoku DK, Smith DC, Browning RA, Jensen RA. Enhanced recognition memory following vagus nerve stimulation in human subjects. Nat Neurosci. 1999 Jan;2(1):94-8.

McLachlan RS, Sadler M, Pillay N, Guberman A, Jones M, Wiebe S, Schneiderman J. Quality of life after vagus nerve stimulation for intractable epilepsy: is seizure control the only contributing factor? Eur Neurol. 2003;50(1):16-9.

Cramer JA, Ben Menachem E, French J. Review of treatment options for refractory epilepsy: new medications and vagal nerve stimulation. Epilepsy Res. 2001 Nov;47(1-2):17-25. Review.

Gilliam FG, Fessler AJ, Baker G, Vahle V, Carter J, Attarian H. Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Neurology. 2004 Jan 13;62(1):23-7.

Responsible Party:	Cyberonics, Inc.
ClinicalTrials.gov Identifier:	NCT00522418 History of Changes
Other Study ID Numbers:	E-100
Study First Received:	August 27, 2007
Results First Received:	April 2, 2010
Last Updated:	October 22, 2012
Health Authority:	Belgium: Institutional Review Board Canada: Ethics Review Committee France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Ethics Commission Italy: Ethics Committee Netherlands: Medical Ethics Review Committee (METC) Norway:National Committee for Medical and Health Research Ethics Spain: Comité Ético de Investigación Clínica Sweden: Regional Ethical Review Board United Kingdom: Research Ethics Committee

Keywords provided by Cyberonics, Inc.:

Epilepsy
VNS Therapy

Additional relevant MeSH terms:

Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on June 18, 2013