External Trigeminal Nerve Stimulation for Epilepsy

Study Overview
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Brief Summary
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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.

Detailed Description
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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: Percent change in seizure frequency during the treatment period compared with the baseline (pre-treatment) period. Time to the 4th seizure The primary comparisons will be between and within groups.

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

Conditions
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Epilepsy, Seizure Disorders

Intervention / Treatment
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* Device: Trigeminal Nerve Stimulation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br> | Device: Trigeminal Nerve Stimulation<br>* External stimulation of the supraorbital branch of the Trigeminal Nerve using a digital TENs unit<br>|
| Other: Control<br> | Device: Trigeminal Nerve Stimulation<br>* External stimulation of the supraorbital branch of the Trigeminal Nerve using a digital TENs unit<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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partial seizures, poorly controlled epilepsy, intractable epilepsy, treatment resistant epilepsy, Trigeminal Nerve, Trigeminal Nerve Stimulation