RNS® System LTT Study

Epilepsy Clinical Trial

Official title:

RNS® System Long-term Treatment (LTT) Clinical Investigation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00572195
• Other study ID #: NP10005
• Secondary ID: P100026
• Status: Completed
• Phase: Phase 4
• Start date: April 2006
• Est. completion date: May 2018

Study information

• Verified date: May 2019
• Source: NeuroPace
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The RNS® System LTT study is designed to assess the ongoing safety and to evaluate the long-term efficacy of the RNS® System as an adjunctive therapy in reducing the frequency of seizures in individuals 18 years of age or older with partial onset seizures that are refractory to two or more antiepileptic medications. Candidates will continue to receive their epilepsy medications while participating in the trial.

Description:

NeuroPace, Inc. is sponsoring an investigational device study of the RNS® System, the first closed loop responsive brain stimulator designed to treat refractory epilepsy. The RNS® System LTT study is an open-label multi-center prospective 7-year clinical investigation which follows completion of the RNS® System Pivotal or Feasibility study. Data regarding safety and efficacy are collected at 6-month intervals, and data regarding quality of life are collected at yearly intervals.

The study is designed to assess the ongoing safety and to evaluate the long-term efficacy of the RNS® System as an adjunctive therapy in reducing the frequency of medically uncontrolled and disabling partial onset seizures that start from one or two areas of the brain.

The RNS® System LTT study will provide additional data on the safety and efficacy of the RNS® System for 7 years following a subject's completion of the RNS® System Feasibility or Pivotal studies. Data from the RNS® System LTT study will be combined with data collected during the RNS® System Feasibility and Pivotal studies, resulting in 9 total years of post-implant follow-up data. These data will be used to calculate long-term SAE rate, percent change in seizure frequency (from pre-implant baseline), as well as the frequency of sudden unexplained death in epilepsy (SUDEP).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: May 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subject has completed either the RNS® System Pivotal or Feasibility study

2. Subject has an implanted RNS® System

3. Subject has elected to continue to receive responsive neurostimulation therapy after completion of the RNS® System Pivotal or Feasibility study

4. Subject is able to attend scheduled appointments for the RNS® System LTT study

Exclusion Criteria:

1. Subject has active psychiatric or medical illness that makes it inadvisable for the subject to continue to receive responsive neurostimulation therapy with the RNS® System

2. Subject has been diagnosed with psychogenic or non-epileptic seizures, or primarily generalized seizures during the RNS® System Pivotal or Feasibility study

3. Subject has been noncompliant with scheduled appointments during the RNS® System Pivotal or Feasibility study

4. Subject has been noncompliant with maintaining seizure diaries during the RNS® System Pivotal or Feasibility study

5. Informed consent cannot be obtained from subject or caregiver

Related Conditions & MeSH terms

• Epilepsy

Intervention

Device:
• RNS® System
The previously implanted RNS® System is programmed to provide responsive stimulation. Upon detecting electrographic patterns, previously identified by the neurologist or neurosurgeon as abnormal, the Neurostimulator provides brief pulses of electrical stimulation through the Leads to interrupt those patterns. Patients with epilepsy treated with responsive direct-brain stimulation with the RNS System typically receive less than 6 minutes of stimulation a day.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Medical College of Georgia / Georgia Regents University	Augusta	Georgia
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Rush University Medical Center / Epilepsy Center	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Florida at Gainesville	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	University of Southern California	Los Angeles	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Miami Children's Hospital	Miami	Florida
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Louisiana State University Epilepsy Center of Excellence	New Orleans	Louisiana
United States	Columbia University / Columbia Presbyterian Medical Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic - Arizona	Phoenix	Arizona
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	California Pacific Medical Center	San Francisco	California
United States	Swedish Medical Center	Seattle	Washington
United States	George Washington University	Washington	District of Columbia
United States	Via Christi Comprehensive Epilepsy Center	Wichita	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
NeuroPace

Country where clinical trial is conducted

United States, 

References & Publications (3)

Bergey GK, Morrell MJ, Mizrahi EM, Goldman A, King-Stephens D, Nair D, Srinivasan S, Jobst B, Gross RE, Shields DC, Barkley G, Salanova V, Olejniczak P, Cole A, Cash SS, Noe K, Wharen R, Worrell G, Murro AM, Edwards J, Duchowny M, Spencer D, Smith M, Gell — View Citation

Heck CN, King-Stephens D, Massey AD, Nair DR, Jobst BC, Barkley GL, Salanova V, Cole AJ, Smith MC, Gwinn RP, Skidmore C, Van Ness PC, Bergey GK, Park YD, Miller I, Geller E, Rutecki PA, Zimmerman R, Spencer DC, Goldman A, Edwards JC, Leiphart JW, Wharen RE, Fessler J, Fountain NB, Worrell GA, Gross RE, Eisenschenk S, Duckrow RB, Hirsch LJ, Bazil C, O'Donovan CA, Sun FT, Courtney TA, Seale CG, Morrell MJ. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial. Epilepsia. 2014 Mar;55(3):432-41. doi: 10.1111/epi.12534. Epub 2014 Feb 22. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Serious Adverse Events (SAE)	The number of subjects having an SAE during the RNS® System LTT study.	2 years post-implant through 9 years post-implant (7 years)
Primary	Percentage Change From Baseline in Seizure Frequency	The average percentage change in the mean frequency of total disabling seizures relative to pre-implant baseline. The percent change will be calculated for each subject over 6-month intervals beginning 6 months after RNS® System implant and continuing through completion of the RNS® System LTT study.	6 months post-implant through 9 years post-implant (8.5 years)
Secondary	Responder Rate	The proportion of subjects with greater than or equal to 50% reduction in total disabling seizures compared to pre-implant baseline.	6 months post-implant through 9 years post-implant (8.5 years)
Secondary	QOLIE (Quality of Life in Epilepsy)	QOLIE 89 (for English-speaking subjects) or QOLIE 31 P (for Spanish speaking subjects) scores collected at each year of follow-up after implantation of the RNS® System compared to the QOLIE 89 / QOLIE 31 P at pre-implant baseline. A QOLIE overall score was obtained using a weighted average of multi-item scale scores. The QOLIE overall score was converted to a T-score, a normally distributed scale with a mean score of 50 and standard deviation (SD) of 10. Higher scores reflect a better quality of life.	1 year post-implant through 9 years post-implant (8 years)
Secondary	Adverse Event Rate	The rate of occurrence of any adverse event (AE) observed during the Long-term Treatment Investigation.	6 months post-implant through 9 years post-implant (8.5 years)