RNS® System Feasibility Study

NCT00079781 | Completed Phase 2 Results DMC

• 1 other identifier: NP10003
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 12

Brief Summary

The RNS® System is intended to treat patients with medically refractory (hard to treat) epilepsy. The RNS® System Feasibility study is designed to demonstrate safety and evidence of effectiveness of the RNS® System to support the commencement of a pivotal clinical investigation.

Conditions

Epilepsy

Keywords

Responsive Stimulation; Brain Stimulator; Epilepsy; Seizures

Outcome Measures

Primary Outcomes (3)

• Acute SAE Rate

  RNS® System Acute SAE Rate = the percentage of subjects having a serious adverse event (SAE) for the surgical implant procedure and the following month (28 days), whether reported as device-related or not. This outcome measure is met when the upper limit of the one-sided 95% confidence interval of the observed RNS® System Acute SAE Rate does not exceed the upper limit of the one-sided 95% confidence interval of the literature-based acute SAE rate associated with the implantation of intracranial electrodes for localization procedures and epilepsy surgery combined as documented in the literature (rate = 19%; upper CI = 28%). The comparator was calculated based upon the literature, therefore the number of participants analyzed is unknown/not applicable. The primary safety outcome measure was met.

  Initial implant through 1 month post-implant

• Short-term Chronic SAE Rate

  The RNS® System Short-term Chronic SAE rate = the percentage of implanted subjects having a serious adverse event (SAE) for the surgical implant procedure and the following 3 months (84 days), whether reported as device-related or not. This outcome measure is met when the upper limit of the one-sided 95% confidence interval of the observed RNS® System Short-term Chronic SAE Rate does not exceed the upper limit of the one-sided 95% confidence interval of the historical short-term chronic SAE rate for deep brain stimulation for movement disorders from the published literature (rate = 36%; upper CI = 46%). The comparator was calculated based upon the literature, therefore the number of participants analyzed is unknown/not applicable. The primary safety outcome measure was met.

  Initial implant through 3 months post-implant

• Responder Rate

  Percentage of subjects with a 50% or greater reduction in mean seizure frequency during the post-implant Evaluation Period (4 months or 112 days) compared to pre-implant baseline (collected during the Prospective Seizure Frequency study). The primary effectiveness endpoint would be met with an observed responder rate of 13% or more. The effectiveness endpoint was only calculated for the Treatment Population. The endpoint was used to support a Pivotal Study, not to demonstrate efficacy when compared to a control/sham group. The primary effectiveness endpoint was met.

  Pre-implant baseline through 4 months post-implant

Study Arms (3)

Treatment Group

ACTIVE COMPARATOR

Group of subjects who have undergone RNS® System implantation who 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 first month post-implant and may continue throughout the subject's participation in the study.

Procedure: RNS® System implantation; Device: RNS® System responsive stimulation

Sham Group

SHAM COMPARATOR

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 Follow-Up Period (5th month post-implant) and may continue for the remainder of the subject's participation in the study.

Procedure: RNS® System implantation

Open Label Group

OTHER

Group of subjects who have undergone RNS® System implantation who were not randomized or blinded to therapy status during the Evaluation Period. Stimulation may have been enabled during the first month post-implant and may have continued throughout the subject's participation in the study.

Procedure: RNS® System implantation; Device: RNS® System responsive stimulation

Interventions

RNS® System implantation PROCEDURE

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.

Open Label Group; Sham Group; Treatment Group

RNS® System responsive stimulation DEVICE

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.

Open Label Group; Treatment Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has simple partial seizures (motor or sensory) or complex partial seizures (with motor manifestations) with or without secondarily generalized seizures
• Subject has seizures that are distinct, stereotypical events that can be reliably counted, in the opinion of the investigator, by the subject or caregiver
• Subject has seizures that are severe enough to cause injuries or significantly impair functional ability in domains including employment, psychosocial, education and mobility
• Subject failed treatment with a minimum of two antiseizure medications (used in appropriate doses) with adequate monitoring of compliance and the effects of treatment
• Subject has remained on the same antiseizure medication(s) over the preceding three (3) months (independent of dose and other than acute, intermittent use of benzodiazepines)
• Subject has a minimum of four (4) or more countable seizures every month over the last three (3) months, as reported from the NeuroPace sponsored Prospective Seizure Frequency Clinical Investigation
• Subject is ≥ 18 years old and ≤ 65 years old
• Subject has undergone diagnostic testing that has established the epileptiform activity onset region(s) as part of his/her standard care to determine candidacy for epilepsy surgery
• Subject is male, or if female is using a reliable method of contraception (hormonal, barrier method, surgical or abstention), or is at least two years postmenopause
• Subject or legal guardian is able to provide appropriate consent to participate
• Subject can be reasonably expected to maintain a seizure diary alone or with the assistance of a competent individual
• Subject is able to complete regular office visits and telephone appointments per the protocol requirements
• Subject is willing to be implanted with the RNS® System as a treatment for his/her seizures
• Subject is able to tolerate a neurosurgical procedure
• Subject is considered a good candidate to be implanted with an RNS® System

You may not qualify if:

• Subject has been diagnosed with psychogenic or non-epileptic seizures in the preceding year
• Subject has been diagnosed with primarily generalized seizures
• Subject has experienced unprovoked status epilepticus in the preceding year
• In the opinion of the investigator, the subject has a clinically significant or unstable medical condition or a progressive central nervous system disease
• Subject has been diagnosed with active psychosis, severe depression or suicidal ideation in the preceding year
• Subject is pregnant or planning on becoming pregnant in the next year
• Subject is on the ketogenic diet
• Subject was enrolled in a therapeutic investigational drug or device study in the preceding year
• Subject has an implanted Vagus Nerve Stimulator (VNS)
• Subject has had therapeutic surgery to treat epilepsy in the preceding year
• Subject is implanted with an electronic medical device that delivers electrical energy to the head or body
• Subject is on chronic anticoagulants or, in the opinion of the investigator, subject is an unsuitable candidate for cranial surgery for any other reason
• Subject had a cranial neurosurgical procedure in the previous month
• Subject requires repeat MRIs
• Subject's seizure onset zone(s) is/are located below the level of the subthalamic nucleus or, in the opinion of the investigator, the necessary lead placement would present too high a risk

Sponsors & Collaborators

• NeuroPace: lead

Study Sites (12)

Mayo Clinic Scottsdale

Phoenix, Arizona, 85054, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

Rush University Medical Center / Epilepsy Center

Chicago, Illinois, 60612, United States

Location

Louisiana State University Epilepsy Center of Excellence

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Columbia University / Columbia Presbyterian Medical Center

New York, New York, 10032, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

Related Publications (1)

• Barkley GL, Smith B, Bergey G, Worrell G, Chabolla D, Drazkowski J, Labar D, Duckrow R, Murro A, Smith M, Gwinn R, Fisch B, Hirsch L, and Morrell M. Safety and Preliminary Efficacy of the RNS Responsive Neurostimulator for the Treatment of Intractable Epilepsy in Adults. Epilepsia 2006; 47(S4):5.

  RESULT

MeSH Terms

Conditions

Epilepsy; Seizures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Martha Morrell, Chief Medical Officer
• Organization: NeuroPace, Inc.

mmorrell@neuropace.com

650-237-2776

Study Officials

• Robert Goodman, MD

  Columbia University / Columbia Presbyterian Medical Center

  PRINCIPAL INVESTIGATOR

• Gregory Barkley, MD

  Henry Ford Hospital

  PRINCIPAL INVESTIGATOR

• Greg Bergey, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Bruce Fisch, MD

  Louisiana State University Epilepsy Center of Excellence

  PRINCIPAL INVESTIGATOR

• Robert Wharen, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Richard Marsh, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Richard Zimmerman, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Anthony Murro, MD

  Augusta University

  PRINCIPAL INVESTIGATOR

• Donna Bergen, MD

  Rush University Medical Center / Epilepsy Center

  PRINCIPAL INVESTIGATOR

• Michael Smith, MD

  Rush University Medical Center / Epilepsy Center

  PRINCIPAL INVESTIGATOR

• Ryder Gwinn, MD

  Swedish Medical Center

  PRINCIPAL INVESTIGATOR

• Douglas Labar, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

• Robert Duckrow, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2004
• First Posted: March 16, 2004
• Study Start: January 1, 2004
• Primary Completion: May 1, 2006
• Study Completion: December 1, 2007
• Last Updated: January 29, 2014
• Results First Posted: December 24, 2013

Record last verified: 2013-12

Locations

US (12)