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

Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00522418
• Other study ID #: E-100
• Status: Terminated
• Phase: Phase 4
• First received: August 27, 2007
• Last updated: January 9, 2015
• Start date: February 2006
• Est. completion date: July 2008

Study information

• Verified date: October 2012
• Source: Cyberonics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Institutional Review BoardCanada: Ethics Review CommitteeFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Ethics CommissionItaly: Ethics CommitteeNetherlands: Medical Ethics Review Committee (METC)Norway:National Committee for Medical and Health Research EthicsSpain: Comité Ético de Investigación ClínicaSweden: Regional Ethical Review BoardUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 122
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 16 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy
• Partial Epilepsy

Intervention

Device:
• Vagal Nerve Simulation (VNS) Therapy
VNS Therapy + Best Medical Practice including anti-epileptic drugs

Drug:
• Best Medical Practive
Best Medical Practice including anti-Epileptic Drugs

Locations

Country	Name	City	State
Belgium	ULB-Hôpital Erasme, Centre de référence pour le traitement de l'épilepsie réfractaire - Neurologie	Brussels
Belgium	UZ Gent, Department of Neurology, 1K12/A	Gent
Canada	Foothills Hospital, Neurology Department	Calgary	Alberta
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Hopital Notre Dame	Montreal	Quebec
Canada	Montreal Neurological Institute, Clinical Research	Montreal	Quebec
France	CHU Grenoble, Neurology Department	Grenoble
France	Hopital Roger Salengro, Service de Neurologie	Lille
France	Hôpital Neurologique, Untité d'épileptologie	Lyon
France	Hôpital Gui De Chauliac, Service Explorations Neurologiques et Epileptologie	Montpellier
France	Hôpital Sainte-Anne, Service de Neurochirurgie	Paris
France	Service d'exploration des épilepsies	Strasbourg
France	CHU Tours, Service de neurologie	Tours
Germany	Universitätskliniken Bonn, Klinik für Epileptologie	Bonn
Germany	Universitätsklinik Erlangen, Zentrum für Epilepsie ZEE	Erlangen
Germany	Klinik der Ernst-Moritz-Arndt-Universität, Neurologische Klinik	Greifswald
Germany	Epilepsiezentrum Kork	Kehl-Kork
Germany	Klinikum der Philips-Universität Marburg, Fachbereich, 20 - Medizin / Klinik Neurologie / Epilepsie Zentrum	Marburg
Germany	Sächsisches Epilepsiezentrum Radeberg, Epilepsiezentrum Kleinwachau	Radeberg
Italy	Azienda Ospedaliero Universitaria - Ospedali Riuniti Umberto I - Lancisi - Salesi, NeuroPsichiatria Infantile	Ancona
Italy	Universita di Bologna, Clinica Neurologica	Bologna
Italy	Azienda Ospendaliero-Universitaria, Caressi Dep Neuroscience	Firenze
Italy	Ospedale San Paolo, Centro Epilessia	Milano
Italy	Universita degli Studi di Cagliari - Policlinico Monserrato, Clinica Neurologica	Monserrato
Italy	Universita di Pisa, Clinica Neurologica	Pisa
Italy	Ospedale F. Lotti, NeuroFisioPatalogia	Pontedera
Italy	Azienda Ospedaliera "Bianchi Melacrino Morelli", Centro Regionale Epilessie	Reggio Calabria
Italy	Università Cattolica Del Sacro Cuore, Istituto di NeuroChirurgia	Roma
Italy	Centro Epilessia, Dipartimento di Neuroscienze	Torino
Netherlands	Tergooiziekenhuizen, Dienst Neurologie	Blaricum
Netherlands	Medisch Spectrum Twente, Dienst Neurologie	Enschede
Netherlands	Stichting Epilepsie Instituut Nederland, Dienst Neurologie	Heemstede
Netherlands	Kempenhaeghe, Dienst Neurologie	Oosterhout
Netherlands	Medisch Centrum Rijnmond-Zuid, locatie Clara, Dienst Neurologie	Rotterdam
Norway	Spesialsykehuset for Epilepsi, Dep of Neurodiagnostics	Sandvika
Spain	Hospital Ruber Internacional, Servicio de neurología	Madrid
Spain	Hospital Clínico de Santiago	Santiago de Compostela
Spain	Hospital Clínico Universitario, Servicio de neurología	Valencia
Spain	Hospital General Basico De La Defensa de Valencia, Servicio de neurología	Valencia
Spain	Hospital General de Valencia, Neurology/Neurophisiology	Valencia
Sweden	Institute of Neuroscience and Physiology, Clinical Neuroscience and Rehabilitation	Goteborg
Sweden	Universitetssjukhuset i Lund, Neurologiska kliniken	Lund
Sweden	Norrlands Universitetssjukhus, Neurocentrum	Umea
Sweden	Akademiska sjukhuset, Neurocentrum	Uppsala
United Kingdom	Addenbrookes Hospital, Dept of Neurosurgery	Cambridge
United Kingdom	Walton Centre, Dept of Neurosciences, Clinical Sciences Centre	Fazakerley
United Kingdom	Kings College Hospital, Dept of Neurosurgery	London
United Kingdom	National Hospital for Neurology and Neurosurgery	London

Sponsors (1)

Lead Sponsor	Collaborator
Cyberonics, Inc.

Countries where clinical trial is conducted

Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Norway,  Spain,  Sweden,  United Kingdom, 

References & Publications (17)

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Ryvlin P, Gilliam FG, Nguyen DK, Colicchio G, Iudice A, Tinuper P, Zamponi N, Aguglia U, Wagner L, Minotti L, Stefan H, Boon P, Sadler M, Benna P, Raman P, Perucca E. The long-term effect of vagus nerve stimulation on quality of life in patients with phar — View Citation

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. — View Citation

Sillanpää 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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Seizure Free Days Over the Last 6 Months		Over the last 6 months	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	Retention Rate	Percent of participants who were compliant with the protocol.	At 12 and 24 months	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No