Clinical trial NCT00522418: Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Epilepsy
Partial Epilepsy
Keywords: Epilepsy
VNS Therapy
Lead sponsor: Cyberonics, Inc.
Sponsor class: INDUSTRY
First posted: 2007-08-29
Enrollment: 122
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Overall Quality of Life in Epilepsy-89 (QOLIE-89) Score in Patients With Baseline & at Least One Post-baseline QOLIE Assessment
timeFrame: Mean change from baseline QOLIE-89 Overall Score at 12 months
Secondary outcomes:
measure: Response Rate
timeFrame: Number of Responders at 12 Months
measure: Percent of Patients That Are Seizure Free
timeFrame: 3, 6, 9, 12, 15, 18, 21, 24 months
measure: Mean Percent Change in Seizure Frequency
timeFrame: Mean percent change from baseline in seizure frequency at 12 months
measure: Seizure Free Days
timeFrame: From the patient's last seizure to the study exit date
measure: Seizure Free Days Over the Last 6 Months
timeFrame: Over the last 6 months
measure: Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Score
timeFrame: Mean change from baseline CES-D Score at 12 months
measure: Change From Baseline in Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score
timeFrame: Mean change from baseline NDDI-E Score at 12 months
measure: Mean Change From Beginning of Intervention Clinical Global Impression-Improvement Scale (CGI-I) Score at 12 Months
timeFrame: Mean change from baseline CGI-I Score at 12 months
measure: Change From Baseline in Adverse Event Profile (AEP) Score
timeFrame: Mean change from baseline AEP Score at 12 months
measure: Changes in Anti-epileptic Drugs (AEDs)
timeFrame: Change from baseline in number of AEDs at 12 months
measure: Retention Rate
timeFrame: At 12 and 24 months
measure: Treatment Emergent Adverse Events, Device Complications, and Premature Study Withdrawal
timeFrame: At 12 and 24 months
measure: Quality of Life in Epilepsy - 89 Items(QOLIE-89)in Patients With Less Than a 50% Reduction in Seizures
timeFrame: At 12 and 24 months
measure: Centre for Epidemiologic Studies Depression Scale (CES-D) in Patients With Less Then a 50% Reduction
timeFrame: At 12 and 24 months
measure: Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) in Patients With Less Then a 50% Reduction in Seizures
timeFrame: At 12 and 24 months
measure: Adverse Event Profile (AEP) in Patients With Less Then a 50% Reduction in Seizures
timeFrame: At 12 and 24 months
measure: Change in the Number of Anti-epileptic Drugs Prescribed
timeFrame: At 12 and 24 months
measure: Percent of Participants Who Were Compliant With the Protocol
timeFrame: At 12 and 24 months
measure: Change From Baseline in QOLIE-89 Measures: Subgroup Analysis of Population With Baseline Adverse Event Profile Score >= 40
timeFrame: Change from baseline up to 12 months
measure: Change From Baseline in QOLIE-89 Measures: Subgroup Analysis of Population With Baseline Adverse Event Profile Score < 40
timeFrame: Change from baseline up to 12 months
measure: Clinical Global Impressions Scale (CGI) in Patients With Less Then a 50% Reduction in Seizures
timeFrame: At 12 and 24 months
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: ULB-Hôpital Erasme, Centre de référence pour le traitement de l'épilepsie réfractaire - Neurologie
city: Gent
country: Belgium
facility: UZ Gent, Department of Neurology, 1K12/A
city: Calgary
country: Canada
facility: Foothills Hospital, Neurology Department
state: Alberta
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Montreal
country: Canada
facility: Hopital Notre Dame
state: Quebec
city: Montreal
country: Canada
facility: Montreal Neurological Institute, Clinical Research
state: Quebec
city: Grenoble
country: France
facility: CHU Grenoble, Neurology Department
city: Lille
country: France
facility: Hopital Roger Salengro, Service de Neurologie
city: Lyon
country: France
facility: Hôpital Neurologique, Untité d'épileptologie
city: Montpellier
country: France
facility: Hôpital Gui De Chauliac, Service Explorations Neurologiques et Epileptologie
city: Paris
country: France
facility: Hôpital Sainte-Anne, Service de Neurochirurgie
city: Strasbourg
country: France
facility: Service d'exploration des épilepsies
city: Tours
country: France
facility: CHU Tours, Service de neurologie
city: Bonn
country: Germany
facility: Universitätskliniken Bonn, Klinik für Epileptologie
city: Erlangen
country: Germany
facility: Universitätsklinik Erlangen, Zentrum für Epilepsie ZEE
city: Greifswald
country: Germany
facility: Klinik der Ernst-Moritz-Arndt-Universität, Neurologische Klinik
city: Kehl-Kork
country: Germany
facility: Epilepsiezentrum Kork
city: Marburg
country: Germany
facility: Klinikum der Philips-Universität Marburg, Fachbereich, 20 - Medizin / Klinik Neurologie / Epilepsie Zentrum
city: Radeberg
country: Germany
facility: Sächsisches Epilepsiezentrum Radeberg, Epilepsiezentrum Kleinwachau
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria - Ospedali Riuniti Umberto I - Lancisi - Salesi, NeuroPsichiatria Infantile
city: Bologna
country: Italy
facility: Universita di Bologna, Clinica Neurologica
city: Firenze
country: Italy
facility: Azienda Ospendaliero-Universitaria, Caressi Dep Neuroscience
city: Milano
country: Italy
facility: Ospedale San Paolo, Centro Epilessia
city: Monserrato
country: Italy
facility: Universita degli Studi di Cagliari - Policlinico Monserrato, Clinica Neurologica
city: Pisa
country: Italy
facility: Universita di Pisa, Clinica Neurologica
city: Pontedera
country: Italy
facility: Ospedale F. Lotti, NeuroFisioPatalogia
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera "Bianchi Melacrino Morelli", Centro Regionale Epilessie
city: Roma
country: Italy
facility: Università Cattolica Del Sacro Cuore, Istituto di NeuroChirurgia
city: Torino
country: Italy
facility: Centro Epilessia, Dipartimento di Neuroscienze
city: Blaricum
country: Netherlands
facility: Tergooiziekenhuizen, Dienst Neurologie
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente, Dienst Neurologie
city: Heemstede
country: Netherlands
facility: Stichting Epilepsie Instituut Nederland, Dienst Neurologie
city: Oosterhout
country: Netherlands
facility: Kempenhaeghe, Dienst Neurologie
city: Rotterdam
country: Netherlands
facility: Medisch Centrum Rijnmond-Zuid, locatie Clara, Dienst Neurologie
city: Sandvika
country: Norway
facility: Spesialsykehuset for Epilepsi, Dep of Neurodiagnostics
city: Madrid
country: Spain
facility: Hospital Ruber Internacional, Servicio de neurología
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico de Santiago
city: Valencia
country: Spain
facility: Hospital Clínico Universitario, Servicio de neurología
city: Valencia
country: Spain
facility: Hospital General de Valencia, Neurology/Neurophisiology
city: Valencia
country: Spain
facility: Hospital General Basico De La Defensa de Valencia, Servicio de neurología
city: Goteborg
country: Sweden
facility: Institute of Neuroscience and Physiology, Clinical Neuroscience and Rehabilitation
city: Lund
country: Sweden
facility: Universitetssjukhuset i Lund, Neurologiska kliniken
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus, Neurocentrum
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset, Neurocentrum
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital, Dept of Neurosurgery
city: Fazakerley
country: United Kingdom
facility: Walton Centre, Dept of Neurosciences, Clinical Sciences Centre
city: London
country: United Kingdom
facility: Kings College Hospital, Dept of Neurosurgery
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery
Study officials:
affiliation: Hopital Neurologique, Lyon, France
name: Phillippe Ryvlin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cyberonics Europe
name: Sophie Leyman, MD
role: STUDY_DIRECTOR
References:
citation: Gilliam F. Optimizing health outcomes in active epilepsy. Neurology. 2002 Apr 23;58(8 Suppl 5):S9-20. doi: 10.1212/wnl.58.8_suppl_5.s9.
citation: Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. doi: 10.1056/NEJM200002033420503.
citation: 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. doi: 10.1056/NEJM199806113382402.
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. doi: 10.1056/NEJM198507183130303.
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. doi: 10.1056/NEJM199209103271104.
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. doi: 10.1212/wnl.47.1.68.
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. doi: 10.1016/s0920-1211(02)00065-7.
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. doi: 10.1111/j.1499-1654.2000.001592.x.
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. doi: 10.1212/wnl.53.8.1731.
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. doi: 10.1212/wnl.57.5.879.
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. doi: 10.1006/ebeh.2000.0046.
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. doi: 10.1016/s0920-1211(00)00181-9.
citation: 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. doi: 10.1038/4600.
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. doi: 10.1159/000070853.
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. doi: 10.1016/s0920-1211(01)00286-8.
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. doi: 10.1212/wnl.62.1.23.
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 pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial. Epilepsia. 2014 Jun;55(6):893-900. doi: 10.1111/epi.12611. Epub 2014 Apr 22.