Epilepsy, Seizures
Conditions
Keywords
Vagus Nerve Stimulation, ASCEND, VNS Titration to Improve Tolerance and Accelerate Adaptation
Brief summary
Post-market, on-label, double-blind, randomized, prospective, interventional, tolerability and clinical outcomes study to determine the number of patients achieving their final assigned VNS Therapy dose settings in patients with drug-resistant epilepsy who are being treated with adjunctive VNS Therapy using new titration protocols.
Detailed description
Post-market, on-label, double-blind, randomized, prospective, interventional, tolerability and clinical outcomes study is designed to determine which VNS Therapy titration paradigm allows more patients to achieve a therapeutic dose within a specified time frame. Additionally, the study will collect data on the acute tolerability and clinical outcomes for patients with drug-resistant epilepsy treated with adjunctive VNS Therapy employing three different titration paradigms.
Interventions
Stimulation of the left tenth cranial nerve via VNS Therapy
Sponsors
Cyberonics, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must agree to be treated with VNS Therapy. The decision to treat with VNS Therapy must have been made independent of and prior to participation in the study. 2. Patients must be 12 years or older and have partial onset seizures or must follow the indication for use statement for VNS Therapy. 3. Patient and/or caregiver must be able and willing to give accurate side effect reports, global impressions data and complete study instruments with minimal assistance throughout the study. 4. Patient or legal guardian understands study procedures and voluntarily signs an informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional policies. In the event the patient is under the age of 18, the patient will also be required to sign an assent affirming agreement to participate in research according to local IRB requirements. 5. Patient must be taking at least 1 anti-epileptic drug treatment
Exclusion criteria
1. Patient currently uses, or is expected to use during the study, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy. 2. Patient is expected to require MRI using a body coil for transmission of RF during the clinical study. 3. Patient has a progressive neurological condition (e.g. brain tumor etc.). 4. In the investigator's opinion, the patient or legal guardian is unable to comply with the frequency of clinic visits during the study. 5. Patient is currently using an investigational device or pharmacologic medication not approved by the FDA. 6. Patient was previously implanted with VNS Therapy. 7. In the investigator's opinion, the patient is considered a suicide risk or is otherwise not a good candidate for this study. 8. Patient/Caregiver is unable to complete the required study follow-up visits and assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Patients Reaching the Defined Target Dose | 12 weeks post implant | Determination of the proportion (percent) of patients in each VNS Therapy titration group reaching the defined target dose within clinically defined titration time-frame |
Countries
United States
Participant flow
Recruitment details
Subjects enrolled at 15 clinical sites including university and private hospital clinics. Enrollment was allowed following successful initiation of the first clinical site on 04MAR2015 and closed on 29JUN2016. The first subject enrolled on 28APR2015 and the final two subjects enrolled on 29JUN2016. The final subject exited the study on 10OCT2016.
Pre-assignment details
All subjects were required to receive implantation of a commercially available Vagus Nerve Stimulation generator (Stimulation of the left tenth cranial nerve via VNS Therapy) prior to randomization. The generator was to remain off until after randomization completion.
Participants by arm
| Arm | Count |
|---|---|
| Group A Vagus Nerve Stimulation Therapy Standard Titration method | 22 |
| Group B Vagus Nerve Stimulation Therapy Alternate Titration 1
Alternate titration method that combined methods from Group A and Group C. | 20 |
| Group C Vagus Nerve Stimulation Therapy Alternate Titration 2
Alternate titration method used in the ANTHEM-HF trial which evaluated the performance of autonomic regulation using VNS Therapy in patients with chronic symptomatic heart failure and reduced ejection fraction. | 20 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Group A | Group B | Group C | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 19 Participants | 19 Participants | 59 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black or African American | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic or Latino | 4 Participants | 2 Participants | 6 Participants | 12 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White Non-Hispanic | 15 Participants | 17 Participants | 13 Participants | 45 Participants |
| Region of Enrollment United States | 22 participants | 20 participants | 20 participants | 62 participants |
| Sex: Female, Male Female | 16 Participants | 11 Participants | 10 Participants | 37 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 10 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 9 / 22 | 7 / 20 | 9 / 20 |
| serious Total, serious adverse events | 0 / 22 | 0 / 20 | 1 / 20 |
Outcome results
Primary
Percent Patients Reaching the Defined Target Dose
Determination of the proportion (percent) of patients in each VNS Therapy titration group reaching the defined target dose within clinically defined titration time-frame
Time frame: 12 weeks post implant
Population: Population of subjects implanted with Vagus Nerve Therapy generator who received stimulation via left, tenth cranial nerve at varying dosing methods (device settings adjustments) depending on the group each subject was randomized. All subject had a common, final target dose to achieve but used alternate methods to achieve the target dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Percent Patients Reaching the Defined Target Dose | 18 Participants |
| Group B | Percent Patients Reaching the Defined Target Dose | 9 Participants |
| Group C | Percent Patients Reaching the Defined Target Dose | 12 Participants |