External Trigeminal Nerve Stimulation for Epilepsy

Randomized Double Blind Study of External Trigeminal Nerve Stimulation for Intractable Epilepsy

This study investigates a new therapy for epilepsy called Trigeminal Nerve Stimulation (TNS). TNS involves external electrical stimulation of sensory nerve located above the eyes and over the forehead. The purpose of this study is to determine if TNS is safe and effective using a rigorous randomized active-control clinical trial design in 50 people with epilepsy.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Seizure Disorders
• Intervention / Treatment: Device: Trigeminal Nerve Stimulation

Detailed Description

Poorly controlled epilepsy is a disabling condition, affecting over one million Americans. Neurostimulation is a promising alternative for patients who have failed medical therapy, and who are not resective surgical candidates.

Trigeminal Nerve Stimulation (TNS) is a novel form of neurostimulation, and has a strong antiepileptic effect in an animal model of seizures. Preliminary data in humans indicates TNS is well tolerated and may be effective in people with intractable epilepsy.

TNS is an alternative mode of neurostimulation, because the Trigeminal Nerve can be stimulated in minimally-invasive fashion.

This is a randomized double blind study of Trigeminal Nerve Stimulation, which compares high stimulation to an active control. Subjects with poorly controlled partial onset seizures who meet all inclusion and exclusion criteria, enter a 6-week baseline period, and then are randomized in double-blind fashion to high or low intensity stimulation for 18 weeks. 50 subjects are to be enrolled at two sites.

Study outcomes are the following:

1. Percent change in seizure frequency during the treatment period compared with the baseline (pre-treatment) period.
2. Time to the 4th seizure

The primary comparisons will be between and within groups.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Department of Neurology
    • Sylmar, California, United States, 91342
      • Olive View/Ucla Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 18 - 70;
• No serious or progressive medical illness;
• A history of intractable partial seizures;
• At least two complex partial or tonic clonic generalized seizures per month in the last two consecutive months;
• MRI or EEG consistent with localization-related or partial epilepsy;
• Exposure to at least two antiepileptic drugs at adequate doses;
• Concurrent use of at least one antiepileptic drug at adequate doses;
• No change in antiepileptic dose for at least 30 days before study enrollment

Exclusion Criteria:

• History of non-epileptic seizures;
• Inability to maintain accurate seizure calendars (self or caregiver);
• Frequent use of benzodiazepines for clusters defined as greater than four times a month;
• History of facial pain or trigeminal neuralgia;
• Concurrent vagus nerve stimulation;
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active	Device: Trigeminal Nerve Stimulation; External stimulation of the supraorbital branch of the Trigeminal Nerve using a digital TENs unit
Other: Control	Device: Trigeminal Nerve Stimulation; External stimulation of the supraorbital branch of the Trigeminal Nerve using a digital TENs unit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
50% Responder Rate	Change in responder rate, at end of study (18 weeks) Absolute percent of subjects with 50% reduction in seizures, 18 weeks compared with 6 weeks Note, the number is not a mean or median, but a fixed percentage.	Treatment period, 18 weeks (end of double blind period) compared with first 6 weeks
Time to the 4th Seizure	Number of Days to the 4th seizure	treatment period (18-weeks)
Change in Seizure Frequency	Percent change in seizure frequency from baseline	18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Ratio: Mean Percent Change in Seizures	Response Ratio: Mean Percent Change in seizures over the treatment period, where [T-B] / [T+B] x 100%, where T = seizure frequency during the treatment period, and B = seizure frequency during the baseline period.	18 weeks
Mood	Mean change in score on the Beck Depression Inventory. The Beck Inventory is a patient reported mood scale. The minimum score is 0, and the maximum score is 63. Scores of less than 10 are considered in the normal range. Scores above 10 are consistent with depression. Higher scores indicate higher degrees of depression, with scores of > 25 consistent with severe depression.	18-weeks

Collaborators and Investigators

• Sponsor: Olive View-UCLA Education & Research Institute
• Collaborators: Boston Scientific Corporation; Epilepsy Foundation
• Investigators: Principal Investigator: Christopher M DeGiorgio, MD, UCLA Department of Neurology; Principal Investigator: Christi Heck, MD, University of Southern California

Publications and helpful links

General Publications

• DeGiorgio CM, Murray D, Markovic D, Whitehurst T. Trigeminal nerve stimulation for epilepsy: long-term feasibility and efficacy. Neurology. 2009 Mar 10;72(10):936-8. doi: 10.1212/01.wnl.0000344181.97126.b4. No abstract available.
• DeGiorgio CM, Soss J, Cook IA, Markovic D, Gornbein J, Murray D, Oviedo S, Gordon S, Corralle-Leyva G, Kealey CP, Heck CN. Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy. Neurology. 2013 Feb 26;80(9):786-91. doi: 10.1212/WNL.0b013e318285c11a. Epub 2013 Jan 30.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: July 7, 2010
• First Submitted That Met QC Criteria: July 8, 2010
• First Posted (Estimate): July 9, 2010

Study Record Updates

• Last Update Posted (Estimate): June 3, 2013
• Last Update Submitted That Met QC Criteria: May 6, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Trigeminal Nerve Stimulation; treatment resistant epilepsy; partial seizures; intractable epilepsy; poorly controlled epilepsy; Trigeminal Nerve
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures
• Other Study ID Numbers: TNS-TDP-01