Epilepsy, Seizure Disorders
Conditions
Keywords
partial seizures, poorly controlled epilepsy, intractable epilepsy, treatment resistant epilepsy, Trigeminal Nerve, Trigeminal Nerve Stimulation
Brief summary
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
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.
Interventions
External stimulation of the supraorbital branch of the Trigeminal Nerve using a digital TENs unit
Sponsors
Epilepsy Foundation
Boston Scientific Corporation
Olive View-UCLA Education & Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 50% Responder Rate | Treatment period, 18 weeks (end of double blind period) compared with first 6 weeks | 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. |
| Time to the 4th Seizure | treatment period (18-weeks) | Number of Days to the 4th seizure |
| Change in Seizure Frequency | 18 weeks | Percent change in seizure frequency from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Ratio: Mean Percent Change in Seizures | 18 weeks | 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. |
| Mood | 18-weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited beginning at Olive View/UCLA and Keck-USC between 3/2008 and 10/2010
Pre-assignment details
6-week pretreatment baseline
Participants by arm
| Arm | Count |
|---|---|
| Active Trigeminal Nerve Stimulation-High Settings | 25 |
| Control Trigeminal Nerve Stimulation-Low Settings | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 3 |
| Overall Study | non-compliance | 1 | 1 |
Baseline characteristics
| Characteristic | Control | Active | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 25 Participants | 50 Participants |
| Age Continuous | 34.2 years STANDARD_DEVIATION 10.81 | 33.1 years STANDARD_DEVIATION 10.57 | 33.44 years STANDARD_DEVIATION 10.58 |
| Region of Enrollment United States | 25 participants | 25 participants | 50 participants |
| Sex: Female, Male Female | 11 Participants | 16 Participants | 27 Participants |
| Sex: Female, Male Male | 14 Participants | 9 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 25 | 4 / 25 |
| serious Total, serious adverse events | 0 / 25 | 1 / 25 |
Outcome results
Primary
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.
Time frame: Treatment period, 18 weeks (end of double blind period) compared with first 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | 50% Responder Rate | 40.5 percentage of participants |
| Control | 50% Responder Rate | 15.6 percentage of participants |
Primary
Change in Seizure Frequency
Percent change in seizure frequency from baseline
Time frame: 18 weeks
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Seizure Frequency | -16.1 percentage change in seizures per month | Standard Deviation 15.4 |
| Control | Change in Seizure Frequency | -10.5 percentage change in seizures per month | Standard Deviation 11.1 |
Primary
Time to the 4th Seizure
Number of Days to the 4th seizure
Time frame: treatment period (18-weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Time to the 4th Seizure | 23 days | Standard Deviation 19 |
| Control | Time to the 4th Seizure | 18 days | Standard Deviation 31 |
| Treatment Group-Baseline | Time to the 4th Seizure | 12.5 days | Standard Deviation 18 |
| Treatment Group-Double Blind Period | Time to the 4th Seizure | 15 days | Standard Deviation 28 |
Secondary
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.
Time frame: 18-weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Mood | -8.13 units on a scale | Standard Deviation 1.35 |
| Control | Mood | -3.95 units on a scale | Standard Deviation 1.22 |
Secondary
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.
Time frame: 18 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Response Ratio: Mean Percent Change in Seizures | -13.9 percentage change of RRATIO | Standard Deviation 6.7 |
| Control | Response Ratio: Mean Percent Change in Seizures | -9.0 percentage change of RRATIO | Standard Deviation 6.8 |