Seizure
Conditions
Keywords
vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, epilepsy, non invasive, gammacore
Brief summary
The purpose of this study is to see the effects of non-invasive vagal nerve stimulation for the reduction in frequency of seizure associated with epilepsy in subjects 18 or older.
Detailed description
The purpose of the study is to determine the effects of non-invasive vagus nerve stimulation for the reduction in frequency of seizure associated with epilepsy in subjects 18 or older. Subjects will record 4 weeks of baseline seizure activity before being randomized for a period of 8 weeks to receive and active treatment to an active-sham treatment. All subjects will then receive another 8 weeks of active treatment.
Interventions
DEVICEgammaCore
vagal verve stimulation 3 times a day 8 hours apart
Sponsors
ElectroCore INC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. The patient is diagnosed with epilepsy with; primary generalized tonic-clonic or partial complex or simple complex or focal onset seizures, with or without secondary generalization. 2. The patient's present antiepileptic drug (AED) therapy is ineffective or intolerable 3. The patient is receiving a stable dose of up to 2 oral AED medication(s) and is not expected to have any change in his/her baseline AED treatment during the treatment period. 4. The patient is having more than 2 recordable seizures a month.
Exclusion criteria
1. The patient has had status epilepticus within the last six months. 2. The patient has had epilepsy surgery or a VNS implant. 3. The patient has had a history or presence of seizures occurring only in clusters (too frequently or indistinctly separated to be reliably counted). 4. The patient has had 4 weeks continuous seizure freedom last 2 months. 5. The patient has psychogenic non-epileptic seizures (PNES) seizures. 6. The patient has a concomitant progressive CNS disease including progressive myoclonus epilepsy. 7. The patient has a significant history of cardiac, renal, neurologic (other than epilepsy), psychiatric, oncologic, endocrinologic, metabolic, or hepatic disease, which would adversely affect their participation in this study. 8. The patient has had an episode of status epilepticus within 4 weeks of Screening. 10\. Has a lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the GammaCore treatment site. 11\. Has known or suspected severe atherosclerotic cardiovascular disease, severe carotid artery disease (e.g. bruits or history of TIA or CVA), congestive heart failure (CHF), known severe coronary artery disease or recent myocardial infarction. 12\. Has an abnormal baseline ECG (e.g. second and third degree heart block, atrial fibrillation, atrial flutter, recent history of ventricular tachycardia or ventricular fibrillation, or clinically significant premature ventricular contraction). 13\. Has had a previous bilateral, right, or left cervical vagotomy. 14. Has uncontrolled high blood pressure. 15. Is currently implanted with an electrical and/or neurostimulator device, including but not limited to cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant. 16\. Has a history of carotid endarterectomy or vascular neck surgery on the right side. 17\. Has been implanted with metal cervical spine hardware or has a metallic implant near the GammaCore stimulation site. 18\. Has a recent or repeated history of syncope. 19. Has a known history or suspicion of substance abuse or addiction. 20. In the opinion of the investigator/research staff the subject is incapable of operating the GammaCore device as intended and performing the data collection procedures. 21\. Is pregnant, nursing, thinking of becoming pregnant in the next 9 months, or of childbearing years and is unwilling to use an accepted form of birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Seizures | 16 weeks | The seizure frequency was collected in the subject diary throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Seizure | 16 weeks | Duration of seizure was recorded by the subject in the subject diary throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). |
| Severity of Seizure | 16 weeks | The Seizure Severity Questionnaire (SSQ) is a self-reported assessment tool, which categorizes seizures into three phases: warning, ictal activity and postictal recovery. The recovery phase is subdivided into three components (cognitive, emotional and physical aspects of recovery), each of which is rated for frequency, severity and bothersome. Overall assessment of seizure severity is measured with the last two items. Items are positively scored from a scale of 1-7, with lower scores representing a better status. 1 = none, never or mild and 7 = extremely frequent, severe or high. The severity was reported for seizures occuring throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). |
| Type of Adverse Events | 16 weeks | Type of adverse events were split in to Adverse Events, Adverse Device Effects and Serious Adverse Events. Adverse events were reported throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). For frequency see the Adverse Event Table. |
| Number of Seizure Free Days | 16 weeks | The number of seizure-free days was collected from the subjects' diary. The total number of days observed days for each phase and the total number of seizure free days for each phase are presented for the course of the study throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). |
| Quality of Life in Epilepsy | 16 weeks | The Quality of Life in Epilepsy-31 (QOLIE-31) instrument is a self- administered questionnaire. It includes seven subscales: Overall Quality of Life, Seizure Worry, Emotional Well-Being, Energy/Fatigue, Cognitive, Medication Effects, and Social Function. Questions 1-30 can yield seven individual scores (per subtest) and a total (composite) score. Higher scores indicate better QOL with values ranging from 1 to 100. Question 31 is a subjective assessment of one's general health condition.Higher scores indicate a better-reported general health condition with the range being 1-10. Scores are presented at end of Intervention 1/Phase 2 (8 weeks) and at the end of Intervention 2/Phase 3 (8 weeks). |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| gammaCore Then Sham gammaCore 8 weeks Active gammaCore stimulation treatment followed by 8 weeks sham (inactive) gammaCore treatment
gammaCore: vagal verve stimulation 3 times a day 8 hours apart | 7 |
| Sham gammaCore Then gammaCore 8 weeks sham (inactive) gammaCore treatment followed by 8 weeks active gammaCore treatment
gammaCore: vagal verve stimulation 3 times a day 8 hours apart | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Randomized Phase 2 | Withdrawal by Subject | 2 | 1 | 0 |
| Randomized Phase 3 | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Sham gammaCore Then gammaCore | gammaCore Then Sham gammaCore | Total |
|---|---|---|---|
| Age, Continuous | 59 years | 43 years | 51 years |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Indian (Fiji) | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 6 Participants | 10 Participants |
| Region of Enrollment Australia | 6 participants | 7 participants | 13 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 7 | 0 / 6 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 6 / 13 | 5 / 7 | 4 / 6 | 2 / 5 | 4 / 5 |
| serious Total, serious adverse events | 0 / 13 | 0 / 7 | 0 / 6 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Frequency of Seizures
The seizure frequency was collected in the subject diary throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks).
Time frame: 16 weeks
Population: safety population 3 subjects were missing data in phase 3 (2 from phase 2 active group and 1 from the phase 2 sham group)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| gammaCore Then Sham gammaCore | Frequency of Seizures | Frequency of Seizure Phase 2 | 9.1 seizures |
| gammaCore Then Sham gammaCore | Frequency of Seizures | Frequency of Seizure Phase 3 | 9.4 seizures |
| Sham gammaCore the gammaCore | Frequency of Seizures | Frequency of Seizure Phase 2 | 8.2 seizures |
| Sham gammaCore the gammaCore | Frequency of Seizures | Frequency of Seizure Phase 3 | 6.6 seizures |
Secondary
Duration of Seizure
Duration of seizure was recorded by the subject in the subject diary throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks).
Time frame: 16 weeks
Population: Safety population. One subject has missing data in the active gammacore group. 2 subjects were missing data in phase 3 (1 from phase 2 active group and 1 from the phase 2 sham group)~1 subject in the phase 3 sham group reported 0 seizures during this phase
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| gammaCore Then Sham gammaCore | Duration of Seizure | Duration of Seizure Phase 2 | 4.5 minutes | Standard Deviation 4.3 |
| gammaCore Then Sham gammaCore | Duration of Seizure | Duration of Seizure Phase 3 | 6.0 minutes | Standard Deviation 8.5 |
| Sham gammaCore the gammaCore | Duration of Seizure | Duration of Seizure Phase 2 | 6.5 minutes | Standard Deviation 10.7 |
| Sham gammaCore the gammaCore | Duration of Seizure | Duration of Seizure Phase 3 | 5.9 minutes | Standard Deviation 7.2 |
Secondary
Number of Seizure Free Days
The number of seizure-free days was collected from the subjects' diary. The total number of days observed days for each phase and the total number of seizure free days for each phase are presented for the course of the study throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks).
Time frame: 16 weeks
Population: Safety population. 1 subject was missing data in the gammacore group.~1 subject from phase 2 gammacore group and 1 subject from the phase 2 sham group were missing data in phase 3
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| gammaCore Then Sham gammaCore | Number of Seizure Free Days | Phase 2 Number of observed seizure free days | 257 days |
| gammaCore Then Sham gammaCore | Number of Seizure Free Days | Phase 3 Number of observed seizure free days | 255 days |
| gammaCore Then Sham gammaCore | Number of Seizure Free Days | Phase 3 Number of observed days (total) | 296 days |
| gammaCore Then Sham gammaCore | Number of Seizure Free Days | Phase 2 Number of observed days (total) | 295 days |
| Sham gammaCore the gammaCore | Number of Seizure Free Days | Phase 2 Number of observed days (total) | 281 days |
| Sham gammaCore the gammaCore | Number of Seizure Free Days | Phase 2 Number of observed seizure free days | 245 days |
| Sham gammaCore the gammaCore | Number of Seizure Free Days | Phase 3 Number of observed days (total) | 270 days |
| Sham gammaCore the gammaCore | Number of Seizure Free Days | Phase 3 Number of observed seizure free days | 244 days |
Secondary
Quality of Life in Epilepsy
The Quality of Life in Epilepsy-31 (QOLIE-31) instrument is a self- administered questionnaire. It includes seven subscales: Overall Quality of Life, Seizure Worry, Emotional Well-Being, Energy/Fatigue, Cognitive, Medication Effects, and Social Function. Questions 1-30 can yield seven individual scores (per subtest) and a total (composite) score. Higher scores indicate better QOL with values ranging from 1 to 100. Question 31 is a subjective assessment of one's general health condition.Higher scores indicate a better-reported general health condition with the range being 1-10. Scores are presented at end of Intervention 1/Phase 2 (8 weeks) and at the end of Intervention 2/Phase 3 (8 weeks).
Time frame: 16 weeks
Population: Safety population. 2 subject in the gammacore group and 1 subject in the sham group were missing data.~1 subject in the gammacore group was missing data in phase 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| gammaCore Then Sham gammaCore | Quality of Life in Epilepsy | Phase 2 Questions 1-30 | 55 units on a scale | Standard Deviation 11.72 |
| gammaCore Then Sham gammaCore | Quality of Life in Epilepsy | Phase 2 Question 31 | 7 units on a scale | Standard Deviation 1.48 |
| gammaCore Then Sham gammaCore | Quality of Life in Epilepsy | Phase 3 Questions 1-30 | 55 units on a scale | Standard Deviation 24.61 |
| gammaCore Then Sham gammaCore | Quality of Life in Epilepsy | Phase 3 Question 31 | 7 units on a scale | Standard Deviation 2.78 |
| Sham gammaCore the gammaCore | Quality of Life in Epilepsy | Phase 3 Question 31 | 6 units on a scale | Standard Deviation 2.19 |
| Sham gammaCore the gammaCore | Quality of Life in Epilepsy | Phase 2 Questions 1-30 | 63 units on a scale | Standard Deviation 19.74 |
| Sham gammaCore the gammaCore | Quality of Life in Epilepsy | Phase 3 Questions 1-30 | 59 units on a scale | Standard Deviation 17.95 |
| Sham gammaCore the gammaCore | Quality of Life in Epilepsy | Phase 2 Question 31 | 6 units on a scale | Standard Deviation 1.95 |
Secondary
Severity of Seizure
The Seizure Severity Questionnaire (SSQ) is a self-reported assessment tool, which categorizes seizures into three phases: warning, ictal activity and postictal recovery. The recovery phase is subdivided into three components (cognitive, emotional and physical aspects of recovery), each of which is rated for frequency, severity and bothersome. Overall assessment of seizure severity is measured with the last two items. Items are positively scored from a scale of 1-7, with lower scores representing a better status. 1 = none, never or mild and 7 = extremely frequent, severe or high. The severity was reported for seizures occuring throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks).
Time frame: 16 weeks
Population: Safety population. 4 subjects were missing data (one in the gammacore group and 3 in the sham group) 3 subjects in the gammacore group were missing data in phase 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| gammaCore Then Sham gammaCore | Severity of Seizure | Severity of Seizure Phase 2 | 4.0 units on a scale | Standard Deviation 2.14 |
| gammaCore Then Sham gammaCore | Severity of Seizure | Severity of Seizure Phase 3 | 4.8 units on a scale | Standard Deviation 2.7 |
| Sham gammaCore the gammaCore | Severity of Seizure | Severity of Seizure Phase 2 | 2.8 units on a scale | Standard Deviation 2.24 |
| Sham gammaCore the gammaCore | Severity of Seizure | Severity of Seizure Phase 3 | 4.0 units on a scale | Standard Deviation 1.49 |
Secondary
Type of Adverse Events
Type of adverse events were split in to Adverse Events, Adverse Device Effects and Serious Adverse Events. Adverse events were reported throughout Intervention 1/Phase 2 (8 weeks) and Intervention 2/Phase 3 (8 weeks). For frequency see the Adverse Event Table.
Time frame: 16 weeks
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gammaCore Then Sham gammaCore | Type of Adverse Events | Adverse Device Effect | 0 Participants |
| gammaCore Then Sham gammaCore | Type of Adverse Events | Serious Adverse Events | 0 Participants |
| gammaCore Then Sham gammaCore | Type of Adverse Events | Adverse Events | 6 Participants |
| Sham gammaCore the gammaCore | Type of Adverse Events | Adverse Events | 5 Participants |
| Sham gammaCore the gammaCore | Type of Adverse Events | Adverse Device Effect | 5 Participants |
| Sham gammaCore the gammaCore | Type of Adverse Events | Serious Adverse Events | 0 Participants |
| Sham Phase 2 | Type of Adverse Events | Adverse Events | 4 Participants |
| Sham Phase 2 | Type of Adverse Events | Adverse Device Effect | 4 Participants |
| Sham Phase 2 | Type of Adverse Events | Serious Adverse Events | 0 Participants |
| gammaCore Phase 3 | Type of Adverse Events | Adverse Device Effect | 2 Participants |
| gammaCore Phase 3 | Type of Adverse Events | Serious Adverse Events | 0 Participants |
| gammaCore Phase 3 | Type of Adverse Events | Adverse Events | 2 Participants |
| Sham Phase 3 | Type of Adverse Events | Adverse Events | 4 Participants |
| Sham Phase 3 | Type of Adverse Events | Adverse Device Effect | 2 Participants |
| Sham Phase 3 | Type of Adverse Events | Serious Adverse Events | 0 Participants |