Clinical trial NCT00215215: Effectiveness Study Comparing Treatment With Drug(s) or Adjunctive VNS Therapy for Pharmacoresistant Partial Seizures
Official title: Post Marketing Study; Randomized, Parallel-Group Comparison of Treatment With Pharmacotherapy or Adjunctive Vagus Nerve Stimulation Therapy for Pharmacoresistant Partial Seizures: A Large Simple Effectiveness Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Epilepsies, Partial
Keywords: Vagus Nerve Stimulation Therapy
Epilepsies, Partial
Seizures
Antiepileptic Drugs
Refractory Partial Seizures
Lead sponsor: Cyberonics, Inc.
Sponsor class: INDUSTRY
First posted: 2005-09-22
Enrollment: 360
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare outcomes over 12 months of treatment with antiepileptic drugs (AEDs) alone or vagus nerve stimulation (VNS) therapy plus AEDs in patients who have partial seizures refractory to at least two, but not more than five, AEDs.

Detailed description: Published data suggest that patients who continue to experience seizures after trials of two or three AEDs are unlikely to become seizure-free with further attempts at pharmacotherapy. Such patients may experience poor quality of life and functional outcomes from continuing seizures and the adverse effects associated with further attempts at pharmacotherapy. VNS is a non-pharmacologic treatment for epilepsy with well-established effectiveness as an adjunctive treatment (to AEDs) for partial seizures refractory to AEDs, but there are no randomized clinical trials comparing the effectiveness of adjunctive VNS therapy with further pharmacotherapy alone in such patients.

Eligibility criteria: Inclusion Criteria:

* Patient has a diagnosis of partial seizures with onset before age 50, and the patient's prior electroencephalography and magnetic resonance imaging studies are consistent with the diagnosis of partial seizures.
* Patient has at least 4 complex partial seizures, but less than 25 seizures (any type), per month during the 3 months preceding randomization; for the 8 weeks preceding randomization, the seizure frequency should be confirmed from a patient diary.
* Patient has not had an adequate response to an adequate dosage of -- or was intolerant to -- a minimum of 2 different AEDs.
* Patient has (in the investigator's judgment) sufficient impairment from his/her epilepsy and/or epilepsy treatment that the potential benefits/risks of VNS therapy are warranted.
* Patient must currently be receiving at least one AED, but not more than three AEDs, in a stable dosage regimen for at least one month before randomization.
* Patient must be 12 years of age or older.
* Patient must be able to provide reliable seizure counts and to complete the evaluations specified in the study procedures flow chart.
* Patient must provide written informed consent, or legal guardian must give written permission and the minor provide written assent.

Exclusion Criteria:

* Patient has a history (lifetime) of having received more than 5 different AEDs.
* Patient has had a bilateral or left cervical vagotomy.
* Patient currently uses, or is expected to use during the study, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy.
* A VNS Therapy System implant would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the patient.
* Patient is expected to require full body magnetic resonance imaging during the clinical study.
* Patient has had a previous VNS Therapy System implant.
* Patient has a previous neuroimaging study that demonstrates mesial temporal sclerosis, cortical dysplasia, or a suspected brain tumor.

Primary outcomes:
measure: *Quality of Life in Epilepsy Questionnaire (QOLIE)
measure: at baseline, Week 26 and Week 52.
measure: *Patients will be asked to keep a daily record of their seizures in a seizure diary supplied by the investigational sites.
Secondary outcomes:
measure: The QOLIE at baseline, Week 26 and Week 52.
measure: *Percentage Change in Seizure-Related Disability Assessment Scale (SERDAS)at baseline and Week 52 for each patient.
measure: *Percentage Change in Hospital Anxiety and Depression Scale (HAD)at baseline and Week 52 for each patient.
measure: *Over the course of the study, AED medications will be assessed.
measure: *Patient Satisfaction Survey will be performed at Week 52.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Bronislav Shafran, M.D., P.C.
state: Arizona
city: Phoenix
country: United States
facility: Xenoscience
state: Arizona
city: Sun City
country: United States
facility: Dedicated Clinical Research, Inc.
state: Arizona
city: Los Angeles
country: United States
facility: USC Comprehensive Epilepsy Center
state: California
city: Roseville
country: United States
facility: Certified Clinical Research
state: California
city: Ventura
country: United States
facility: Pediatric Diagnostic Center
state: California
city: Gainesville
country: United States
facility: University of Florida, Department of Neurology
state: Florida
city: Maitland
country: United States
facility: Neurology Associates, P.A.
state: Florida
city: Pensacola
country: United States
facility: Child Neurology Center of Northwest Florida
state: Florida
city: Boise
country: United States
facility: Pediatric Neurology of Idaho
state: Idaho
city: Freeport
country: United States
facility: Freeport Health Network, Department of Neurology
state: Illinois
city: Detroit
country: United States
facility: Wayne State University School of Medicine, Department of Neurology
state: Michigan
city: New York
country: United States
facility: Weill-Cornell Medical College, N.Y. Presbyterian Hospital, Comprehensive Epilepsy Center
state: New York
city: Asheville
country: United States
facility: William Huffstutter, M.D.
state: North Carolina
city: Medford
country: United States
facility: Medford Neurological and Spine Clinic
state: Oregon
city: Bethlehem
country: United States
facility: Neurology and Sleep Medicine
state: Pennsylvania
city: Germantown
country: United States
facility: Mid-South Physicians Group, P.L.L.C.
state: Tennessee
city: Houston
country: United States
facility: Hermann Hospital, UT Comprehensive Epilepsy Center
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: San Antonio
country: United States
facility: Texas Association of Pediatric Neurology
state: Texas
city: Midvale
country: United States
facility: Pivotal Research Centers
state: Utah
city: South Ogden
country: United States
facility: Pharmaceutical Research Organization
state: Utah
city: Milwaukee
country: United States
facility: Regional Epilepsy Center Saint Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Cyberonics, Inc.
name: Carol C Base, RN, MS
role: STUDY_DIRECTOR
References:
citation: Schachter SC. Vagus nerve stimulation therapy summary: five years after FDA approval. Neurology. 2002 Sep 24;59(6 Suppl 4):S15-20. doi: 10.1212/wnl.59.6_suppl_4.s15.
citation: Renfroe JB, Wheless JW. Earlier use of adjunctive vagus nerve stimulation therapy for refractory epilepsy. Neurology. 2002 Sep 24;59(6 Suppl 4):S26-30. doi: 10.1212/wnl.59.6_suppl_4.s26.
citation: Fisher RS, Handforth A. Reassessment: vagus nerve stimulation for epilepsy [RETIRED]: a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 1999 Sep 11;53(4):666-9. doi: 10.1212/wnl.53.4.666. No abstract available.
citation: Heck C, Helmers SL, DeGiorgio CM. Vagus nerve stimulation therapy, epilepsy, and device parameters: scientific basis and recommendations for use. Neurology. 2002 Sep 24;59(6 Suppl 4):S31-7. doi: 10.1212/wnl.59.6_suppl_4.s31.