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

NCT00522418 | Terminated Phase 4 Results DMC

• 1 other identifier: E-100
• Study Type: interventional
• Target: 122
• Locations: 10 countries
• Sites: 48

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.

Conditions

Epilepsy; Partial Epilepsy

Keywords

Epilepsy; VNS Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (21)

• Response Rate

  Number of Responders at 12 Months

• Percent of Patients That Are Seizure Free

  3, 6, 9, 12, 15, 18, 21, 24 months

• Mean Percent Change in Seizure Frequency

  Mean percent change from baseline in seizure frequency at 12 months

• Seizure Free Days

  From the patient's last seizure to the study exit date

• Seizure Free Days Over the Last 6 Months

  Over the last 6 months

Study Arms (2)

VNS Therapy

EXPERIMENTAL

VNS Therapy + Best Medical Practice

Device: Vagal Nerve Simulation (VNS) Therapy

Best Medical Practice

ACTIVE COMPARATOR

Best Medical Practice

Drug: Best Medical Practive

Interventions

Vagal Nerve Simulation (VNS) Therapy DEVICE

VNS Therapy + Best Medical Practice including anti-epileptic drugs

VNS Therapy

Best Medical Practive DRUG

Best Medical Practice including anti-Epileptic Drugs

Best Medical Practice

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Cyberonics, Inc.: lead

Study Sites (48)

ULB-Hôpital Erasme, Centre de référence pour le traitement de l'épilepsie réfractaire - Neurologie

Brussels, 1070, Belgium

Location

UZ Gent, Department of Neurology, 1K12/A

Ghent, 9000, Belgium

Location

Foothills Hospital, Neurology Department

Calgary, Alberta, T1Y6J4, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Hopital Notre Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Montreal Neurological Institute, Clinical Research

Montreal, Quebec, H3A 2B4, Canada

Location

CHU Grenoble, Neurology Department

Grenoble, 38043, France

Location

Hopital Roger Salengro, Service de Neurologie

Lille, 59037, France

Location

Hôpital Neurologique, Untité d'épileptologie

Lyon, 69003, France

Location

Hôpital Gui De Chauliac, Service Explorations Neurologiques et Epileptologie

Montpellier, 34295, France

Location

Hôpital Sainte-Anne, Service de Neurochirurgie

Paris, 75674, France

Location

Service d'exploration des épilepsies

Strasbourg, 67091, France

Location

CHU Tours, Service de neurologie

Tours, 37044, France

Location

Universitätskliniken Bonn, Klinik für Epileptologie

Bonn, 53105, Germany

Location

Universitätsklinik Erlangen, Zentrum für Epilepsie ZEE

Erlangen, 91054, Germany

Location

Klinik der Ernst-Moritz-Arndt-Universität, Neurologische Klinik

Greifswald, 17487, Germany

Location

Epilepsiezentrum Kork

Kehl-Kork, 77694, Germany

Location

Klinikum der Philips-Universität Marburg, Fachbereich, 20 - Medizin / Klinik Neurologie / Epilepsie Zentrum

Marburg, 35039, Germany

Location

Sächsisches Epilepsiezentrum Radeberg, Epilepsiezentrum Kleinwachau

Radeberg, 01465, Germany

Location

Azienda Ospedaliero Universitaria - Ospedali Riuniti Umberto I - Lancisi - Salesi, NeuroPsichiatria Infantile

Ancona, 60100, Italy

Location

Universita di Bologna, Clinica Neurologica

Bologna, 40123, Italy

Location

Azienda Ospendaliero-Universitaria, Caressi Dep Neuroscience

Florence, 50100, Italy

Location

Ospedale San Paolo, Centro Epilessia

Milan, 20142, Italy

Location

Universita degli Studi di Cagliari - Policlinico Monserrato, Clinica Neurologica

Monserrato, 09042, Italy

Location

Universita di Pisa, Clinica Neurologica

Pisa, 56126, Italy

Location

Ospedale F. Lotti, NeuroFisioPatalogia

Pontedera, 56025, Italy

Location

Azienda Ospedaliera "Bianchi Melacrino Morelli", Centro Regionale Epilessie

Reggio Calabria, 89100, Italy

Location

Università Cattolica Del Sacro Cuore, Istituto di NeuroChirurgia

Roma, 00168, Italy

Location

Centro Epilessia, Dipartimento di Neuroscienze

Torino, 10126, Italy

Location

Tergooiziekenhuizen, Dienst Neurologie

Blaricum, 1261, AN, Netherlands

Location

Medisch Spectrum Twente, Dienst Neurologie

Enschede, 7513 R, Netherlands

Location

Stichting Epilepsie Instituut Nederland, Dienst Neurologie

Heemstede, 8025 BV, Netherlands

Location

Kempenhaeghe, Dienst Neurologie

Oosterhout, 4901 ZG, Netherlands

Location

Medisch Centrum Rijnmond-Zuid, locatie Clara, Dienst Neurologie

Rotterdam, 3078 HT, Netherlands

Location

Spesialsykehuset for Epilepsi, Dep of Neurodiagnostics

Sandvika, 1306, Norway

Location

Hospital Ruber Internacional, Servicio de neurología

Madrid, 28034, Spain

Location

Hospital Clínico de Santiago

Santiago de Compostela, 15706, Spain

Location

Hospital Clínico Universitario, Servicio de neurología

Valencia, 46010, Spain

Location

Hospital General de Valencia, Neurology/Neurophisiology

Valencia, 46014, Spain

Location

Hospital General Basico De La Defensa de Valencia, Servicio de neurología

Valencia, 46930, Spain

Location

Institute of Neuroscience and Physiology, Clinical Neuroscience and Rehabilitation

Gothenburg, 41345, Sweden

Location

Universitetssjukhuset i Lund, Neurologiska kliniken

Lund, 221 85, Sweden

Location

Norrlands Universitetssjukhus, Neurocentrum

Umeå, 901 85, Sweden

Location

Akademiska sjukhuset, Neurocentrum

Uppsala, 751 85, Sweden

Location

Addenbrookes Hospital, Dept of Neurosurgery

Cambridge, CB2 2QQ, United Kingdom

Location

Walton Centre, Dept of Neurosciences, Clinical Sciences Centre

Fazakerley, L97LJ, United Kingdom

Location

Kings College Hospital, Dept of Neurosurgery

London, SE5 9RS, United Kingdom

Location

National Hospital for Neurology and Neurosurgery

London, WC1N3B, United Kingdom

Location

Related Publications (17)

• 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.

  PMID: 11971128 BACKGROUND

• Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. doi: 10.1056/NEJM200002033420503.

  PMID: 10660394 BACKGROUND

• 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.

  PMID: 9624191 BACKGROUND

• 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.

  PMID: 3925335 BACKGROUND

• 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.

  PMID: 1298221 BACKGROUND

• 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.

  PMID: 8710127 BACKGROUND

• 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.

  PMID: 12151114 BACKGROUND

• 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.

  PMID: 11114218 BACKGROUND

• 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.

  PMID: 10563620 BACKGROUND

• 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.

  PMID: 11552020 BACKGROUND

• 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.

  PMID: 12609137 BACKGROUND

• 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.

  PMID: 11074193 BACKGROUND

• 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.

  PMID: 10195186 BACKGROUND

• 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.

  PMID: 12824707 BACKGROUND

• 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.

  PMID: 11673017 BACKGROUND

• 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.

  PMID: 14718691 BACKGROUND

• 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.

  PMID: 24754318 RESULT

MeSH Terms

Conditions

Epilepsy; Epilepsies, Partial

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

This study was terminated as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Results Point of Contact

• Title: Mark Bunker, Senior Director, Global Medical Affairs
• Organization: Cyberonics, Inc

Mark.Bunker@cyberonics.com

281-228-7223

Study Officials

• Phillippe Ryvlin, MD

  Hopital Neurologique, Lyon, France

  PRINCIPAL INVESTIGATOR

• Sophie Leyman, MD

  Cyberonics Europe

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2007
• First Posted: August 29, 2007
• Study Start: February 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: January 26, 2015
• Results First Posted: May 17, 2010

Record last verified: 2012-10

Locations

NL (5); SE (4); NO (1); FR (7); GB (4); ES (5); CA (4); BE (2); DE (6); IT (10)