Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
240 participants
INTERVENTIONAL
2005-12-31
2011-05-31
Brief Summary
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Detailed Description
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The RNS® Neurostimulator (a pacemaker-like device) and NeuroPace® Leads (tiny wires with electrodes) are implanted in the head. The Neurostimulator is a battery powered, microprocessor controlled device that detects and stores records of electrographic patterns (such as epileptiform, or seizure-like, activity) from the Leads within the brain. When the device detects an electrographic pattern, it responds by sending electrical stimulation through the Leads to a small part of the patient's brain to interrupt the electrographic pattern. This type of treatment is called responsive stimulation, but it is not yet known if it will work for the treatment of epilepsy. Direct brain stimulation therapy has already received approval in the United States, Europe, Canada, and Australia for the treatment of Essential Tremor and Parkinson's disease. Direct brain stimulation is not approved for the treatment of epilepsy.
Subjects participating in the RNS® System Pivotal study must met inclusion criteria, including localization of epileptogenic region(s), prior to enrolling in the study. Throughout the entire study, subjects or their caregivers must keep a seizure diary. Seizure frequency, seizure severity, and antiepileptic medications, as well as physical and emotional health will be monitored and recorded throughout the study.
Upon demonstrating the required seizure frequency and stable antiepileptic medications over 3 consecutive months of the Baseline (pre-implant) Period, subjects will qualify for RNS® System implantation. Antiepileptic medications should continue to remain stable until 6 months post-implant. The surgical procedure will be performed within one month of qualification.
The RNS® Neurostimulator is cranially implanted and connected to one or two NeuroPace® Leads implanted in the brain. The investigational team will determine the placement of the Leads based on prior localization of the epileptogenic region, according to standard localization procedures. Detection of epileptiform activity will be enabled for all subjects during the 1 month Post-Operative Stabilization Period. Subjects will be randomized 1:1 to either the Treatment or Sham group prior to starting the 1 month Stimulation Optimization Period. During this period subjects are seen on a weekly basis by the Treatment Protocol investigator. Responsive stimulation will be enabled and optimized for subjects randomized to the Treatment group. Subjects randomized to the Sham group will be seen for simulated stimulation programming in order to maintain the treatment blind.
The Blinded Evaluation Period is comprised of months 3, 4, and 5 post-implant. Subjects in the Treatment group will receive responsive stimulation and subjects in the Sham group will not. Subjects will not know whether responsive stimulation is being delivered or not. At the end of the 5th month, all subjects' transition into the Open Label Evaluation Period during which all subjects may receive responsive stimulation and antiepileptic medications may be adjusted as medically required.
Subjects will be followed for 2 years post-implant. Throughout study participation, both effectiveness and safety data will be monitored continuously, and reviewed and documented by the study investigator at study appointments scheduled every month for the first year post-implant, then every 3 months.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Treatment Group (stimulation ON)
Group of subjects that have undergone RNS® System implantation that are randomized to receive RNS® System responsive stimulation (i.e. responsive stimulation enabled or turned ON) during the Blinded Evaluation Period. Stimulation is enabled during the Stimulation Optimization Period (second month post-implant) and may continue throughout the subject's participation in the study.
RNS® System implantation
Using standard neurosurgical techniques the surgical team implants the RNS® System, which includes the RNS® Neurostimulator and intracranial NeuroPace® Leads. Up to 4 Leads (Cortical Strips and/or Depth Leads) are placed in or near the epileptogenic focus/foci. The Neurostimulator is placed in the skull and connected to up to 2 Leads. At first the Neurostimulator is programmed to record brain activity (electrographic patterns). The neurologist or neurosurgeon reviews the recorded electrographic patterns and identifies abnormal (epileptiform, or seizure-like) activity. The Neurostimulator is then programmed to detect the abnormal activity.
RNS® System responsive stimulation
The RNS® System is programmed to provide responsive stimulation (stimulation is ON or enabled). Upon detecting electrographic patterns, previously identified by the neurologist or neurosurgeon as abnormal (epileptiform, or seizure-like) activity, the Neurostimulator provides brief pulses of electrical stimulation through the Leads to interrupt those patterns. The typical patient is treated with a cumulative total of 5 minutes of stimulation a day.
Sham Group (stimulation OFF)
Group of subjects that have undergone RNS® System implantation that are randomized to receive sham-stimulation (i.e. responsive stimulation disabled or turned OFF) during the Blinded Evaluation Period. Stimulation is enabled after transition into the Open Label Period (sixth month post-implant) and may continue for the remainder of the subject's participation in the study.
RNS® System implantation
Using standard neurosurgical techniques the surgical team implants the RNS® System, which includes the RNS® Neurostimulator and intracranial NeuroPace® Leads. Up to 4 Leads (Cortical Strips and/or Depth Leads) are placed in or near the epileptogenic focus/foci. The Neurostimulator is placed in the skull and connected to up to 2 Leads. At first the Neurostimulator is programmed to record brain activity (electrographic patterns). The neurologist or neurosurgeon reviews the recorded electrographic patterns and identifies abnormal (epileptiform, or seizure-like) activity. The Neurostimulator is then programmed to detect the abnormal activity.
Interventions
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RNS® System implantation
Using standard neurosurgical techniques the surgical team implants the RNS® System, which includes the RNS® Neurostimulator and intracranial NeuroPace® Leads. Up to 4 Leads (Cortical Strips and/or Depth Leads) are placed in or near the epileptogenic focus/foci. The Neurostimulator is placed in the skull and connected to up to 2 Leads. At first the Neurostimulator is programmed to record brain activity (electrographic patterns). The neurologist or neurosurgeon reviews the recorded electrographic patterns and identifies abnormal (epileptiform, or seizure-like) activity. The Neurostimulator is then programmed to detect the abnormal activity.
RNS® System responsive stimulation
The RNS® System is programmed to provide responsive stimulation (stimulation is ON or enabled). Upon detecting electrographic patterns, previously identified by the neurologist or neurosurgeon as abnormal (epileptiform, or seizure-like) activity, the Neurostimulator provides brief pulses of electrical stimulation through the Leads to interrupt those patterns. The typical patient is treated with a cumulative total of 5 minutes of stimulation a day.
Eligibility Criteria
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Inclusion Criteria
2. Subject's seizures are distinct, stereotypical events that can be reliably counted.
3. Subject failed treatment with a minimum of 2 anti-seizure medications.
4. Subject has remained on the same antiepileptic medication(s) over the 3 most recent consecutive months (other than acute, intermittent use of benzodiazepines). Subjects on the ketogenic diet are permitted if the diet has been stable for the preceding 3 months.
5. Subject reports having an average of 3 or more disabling motor simple partial seizures, complex partial seizures and/or secondarily generalized seizures per month over the 3 most recent consecutive months, with no month with less than 2 seizures.
6. Subject is between the ages of 18 and 70 years.
7. Subject has undergone diagnostic testing that has identified no more than 2 epileptogenic regions.
8. Subject is male or a female of childbearing potential using a reliable method of contraception or is at least two years post-menopause.
9. Subject or legal guardian is able to provide appropriate consent to participate.
10. Subject can be reasonably expected to maintain a seizure diary alone or with the assistance of a competent individual.
11. Subject is able to complete regular office and telephone appointments per the protocol requirements.
12. Subject is willing to be implanted with the RNS® System as a treatment for his/her seizures.
13. Subject is able to tolerate a neurosurgical procedure.
14. Subject is considered a good candidate to be implanted with the RNS® System.
Note: A subject is still eligible to participate if antiepileptic medication(s) were temporarily discontinued for the purposes of diagnostic or medical procedures during the preceding 3 months.
Exclusion Criteria
2. Subject has been diagnosed with primarily generalized seizures.
3. Subject has experienced unprovoked status epilepticus in the preceding year.
4. Subject has a clinically significant or unstable medical condition (including alcohol and/or drug abuse) or a progressive central nervous system disease.
5. Subject is taking chronic anticoagulants.
6. Subject has been diagnosed with active psychosis, major depression or suicidal ideation in the preceding year. Subjects with post-ictal psychiatric symptoms need not be excluded.
7. Subject is pregnant or planning on becoming pregnant in the next 2 years.
8. Subject is enrolled in a therapeutic investigational drug or device trial.
9. Subject has an implanted Vagus Nerve Stimulator (VNS) or is unwilling to have the VNS explanted. (VNS therapy must have been discontinued for at least 3 months prior to enrollment.)
10. Subject has had therapeutic surgery to treat epilepsy in the preceding 6 months.
11. Subject has had a cranial neurosurgical procedure (including endovascular procedures) other than an epilepsy surgery involving the skull or brain in the previous month.
12. Subject is implanted with an electronic medical device that delivers electrical energy to the head.
13. Subject is an unsuitable candidate for neurosurgery.
14. Subject requires repeat MRIs in which the head is exposed to the radio frequency field.
15. Subject's epileptogenic region(s) is/are located caudal to the level of the thalamus.
16. Implantation of the RNS® Neurostimulator and Lead(s) would present unacceptable risk.
18 Years
70 Years
ALL
No
Sponsors
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NeuroPace
INDUSTRY
Responsible Party
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Principal Investigators
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Gregory Barkley, MD
Role: PRINCIPAL_INVESTIGATOR
Johns Hopkins University
Michel Berg, MD
Role: PRINCIPAL_INVESTIGATOR
University of Rochester
Gregory Bergey, MD
Role: PRINCIPAL_INVESTIGATOR
Henry Ford Hospital
Carl Bazil, MD
Role: PRINCIPAL_INVESTIGATOR
Columbia University / Columbia Presbyterian Medical Center
Andrew Cole, MD
Role: PRINCIPAL_INVESTIGATOR
Massachusetts General Hospital
Michael Duchowny, MD
Role: PRINCIPAL_INVESTIGATOR
Nicklaus Children's Hospital f/k/a Miami Children's Hospital
Robert Duckrow, MD
Role: PRINCIPAL_INVESTIGATOR
Yale University
Jonathan Edwards, MD
Role: PRINCIPAL_INVESTIGATOR
Medical University of South Carolina
Stephan Eisenschenk, MD
Role: PRINCIPAL_INVESTIGATOR
University of Florida at Gainesville
A. James Fessler, MD
Role: PRINCIPAL_INVESTIGATOR
University of Rochester
Nathan Fountain, MD
Role: PRINCIPAL_INVESTIGATOR
University of Virginia
Eric Geller, MD
Role: PRINCIPAL_INVESTIGATOR
St. Barnabas Medical Center
Robert Gross, MD
Role: PRINCIPAL_INVESTIGATOR
Emory University
Ryder Gwinn, MD
Role: PRINCIPAL_INVESTIGATOR
Swedish Medical Center
Christianne Heck, MD
Role: PRINCIPAL_INVESTIGATOR
University of Southern California
Barbara Jobst, MD
Role: PRINCIPAL_INVESTIGATOR
Dartmouth-Hitchcock Medical Center
David King-Stephens, MD
Role: PRINCIPAL_INVESTIGATOR
California Pacific Medical Center
James Leiphart, MD
Role: PRINCIPAL_INVESTIGATOR
George Washington University
W. Richard Marsh, MD
Role: PRINCIPAL_INVESTIGATOR
Mayo Clinic
Andrew Massey, MD
Role: PRINCIPAL_INVESTIGATOR
Via Christi Comprehensive Epilepsy Center
Eli Mizrahi, MD
Role: PRINCIPAL_INVESTIGATOR
Baylor College of Medicine
Dileep Nair, MD
Role: PRINCIPAL_INVESTIGATOR
The Cleveland Clinic
Cormac O'Donovan, MD
Role: PRINCIPAL_INVESTIGATOR
Wake Forest University Health Sciences
A. LeBron Paige, MD
Role: PRINCIPAL_INVESTIGATOR
University of Alabama at Birmingham
Yong Park, MD
Role: PRINCIPAL_INVESTIGATOR
Medical College of Georgia / Georgia Health Sciences University
Paul Rutecki, MD
Role: PRINCIPAL_INVESTIGATOR
University of Wisconsin, Madison
Vicenta Salanova, MD
Role: PRINCIPAL_INVESTIGATOR
Indiana University
Christopher Skidmore, MD
Role: PRINCIPAL_INVESTIGATOR
Thomas Jefferson University
Michael Smith, MD
Role: PRINCIPAL_INVESTIGATOR
Rush University Medical Center / Epilepsy Center
David Spencer, MD
Role: PRINCIPAL_INVESTIGATOR
Oregon Health and Science University
Paul Van Ness, MD
Role: PRINCIPAL_INVESTIGATOR
University of Texas Southwestern Medical Center
Robert Wharen, MD
Role: PRINCIPAL_INVESTIGATOR
Mayo Clinic
Richard Zimmerman, MD
Role: PRINCIPAL_INVESTIGATOR
Mayo Clinic
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Mayo Clinic - Arizona
Phoenix, Arizona, United States
University of Southern California
Los Angeles, California, United States
California Pacific Medical Center
San Francisco, California, United States
Yale University School of Medicine
New Haven, Connecticut, United States
George Washington University
Washington D.C., District of Columbia, United States
University of Florida at Gainesville
Gainesville, Florida, United States
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States
Miami Children's Hospital
Miami, Florida, United States
Emory University
Atlanta, Georgia, United States
Medical College of Georgia / Georgia Health Sciences University
Augusta, Georgia, United States
Rush University Medical Center/ Epilepsy Center
Chicago, Illinois, United States
Indiana University
Indianapolis, Indiana, United States
Via Christi Comprehensive Epilepsy Center
Wichita, Kansas, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
Mayo Clinic - Rochester
Rochester, Minnesota, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
Saint Barnabas Medical Center
Livingston, New Jersey, United States
Columbia University / Columbia Presbyterian Medical Center
New York, New York, United States
University of Rochester
Rochester, New York, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Oregon Health & Science University
Portland, Oregon, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Baylor College of Medicine
Houston, Texas, United States
University of Virginia
Charlottesville, Virginia, United States
Swedish Medical Center
Seattle, Washington, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Countries
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References
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Behrens E, Schramm J, Zentner J, Konig R. Surgical and neurological complications in a series of 708 epilepsy surgery procedures. Neurosurgery. 1997 Jul;41(1):1-9; discussion 9-10. doi: 10.1097/00006123-199707000-00004.
Beric A, Kelly PJ, Rezai A, Sterio D, Mogilner A, Zonenshayn M, Kopell B. Complications of deep brain stimulation surgery. Stereotact Funct Neurosurg. 2001;77(1-4):73-8. doi: 10.1159/000064600.
Fountas KN, Smith JR. A novel closed-loop stimulation system in the control of focal, medically refractory epilepsy. Acta Neurochir Suppl. 2007;97(Pt 2):357-62. doi: 10.1007/978-3-211-33081-4_41.
Fountas KN, Smith JR. Subdural electrode-associated complications: a 20-year experience. Stereotact Funct Neurosurg. 2007;85(6):264-72. doi: 10.1159/000107358. Epub 2007 Aug 17.
Hamer HM, Morris HH, Mascha EJ, Karafa MT, Bingaman WE, Bej MD, Burgess RC, Dinner DS, Foldvary NR, Hahn JF, Kotagal P, Najm I, Wyllie E, Luders HO. Complications of invasive video-EEG monitoring with subdural grid electrodes. Neurology. 2002 Jan 8;58(1):97-103. doi: 10.1212/wnl.58.1.97.
Hariz MI. Complications of deep brain stimulation surgery. Mov Disord. 2002;17 Suppl 3:S162-6. doi: 10.1002/mds.10159.
Joint C, Nandi D, Parkin S, Gregory R, Aziz T. Hardware-related problems of deep brain stimulation. Mov Disord. 2002;17 Suppl 3:S175-80. doi: 10.1002/mds.10161.
Koller WC, Lyons KE, Wilkinson SB, Troster AI, Pahwa R. Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor. Mov Disord. 2001 May;16(3):464-8. doi: 10.1002/mds.1089.
Oh MY, Abosch A, Kim SH, Lang AE, Lozano AM. Long-term hardware-related complications of deep brain stimulation. Neurosurgery. 2002 Jun;50(6):1268-74; discussion 1274-6. doi: 10.1097/00006123-200206000-00017.
Tanriverdi T, Ajlan A, Poulin N, Olivier A. Morbidity in epilepsy surgery: an experience based on 2449 epilepsy surgery procedures from a single institution. J Neurosurg. 2009 Jun;110(6):1111-23. doi: 10.3171/2009.8.JNS08338.
Wong CH, Birkett J, Byth K, Dexter M, Somerville E, Gill D, Chaseling R, Fearnside M, Bleasel A. Risk factors for complications during intracranial electrode recording in presurgical evaluation of drug resistant partial epilepsy. Acta Neurochir (Wien). 2009 Jan;151(1):37-50. doi: 10.1007/s00701-008-0171-7. Epub 2009 Jan 8.
Morrell MJ; RNS System in Epilepsy Study Group. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology. 2011 Sep 27;77(13):1295-304. doi: 10.1212/WNL.0b013e3182302056. Epub 2011 Sep 14.
Meador KJ, Kapur R, Loring DW, Kanner AM, Morrell MJ; RNS(R) System Pivotal Trial Investigators. Quality of life and mood in patients with medically intractable epilepsy treated with targeted responsive neurostimulation. Epilepsy Behav. 2015 Apr;45:242-7. doi: 10.1016/j.yebeh.2015.01.012. Epub 2015 Mar 26.
Other Identifiers
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NP10004
Identifier Type: -
Identifier Source: org_study_id