Chronic Migraine
Conditions
Keywords
vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, chronic migraine, migraine, non invasive, gammacore
Brief summary
The purpose of this multi-center, prospective, double-blind, randomized, sham-controlled pilot study is to study feasibility and collect preliminary clinical data related to the safety and clinical benefits of daily use of non-invasive vagal nerve stimulation with the GammaCore device for the prevention of chronic migraine, and to support the development and approval of a larger pivotal study.
Interventions
DEVICEGammaCore Active Device
DEVICEGammaCore Sham Device
Sponsors
ElectroCore INC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Is between the ages of 18 and 65 years. * Has been previously diagnosed as suffering from migraine, in accordance with the ICHD-2 Classification criteria (2nd), with or without aura. * Experiences at least 15 headache days per month (over the last 3 months). * Has age of onset of migraine less than 50 years old. * Agrees not to use any migraine prevention treatments (including Botox injections) and/or medications (exclusive of medications taken for acute relief of migraine symptoms). * Is able to provide written Informed Consent * Agrees to refrain from changing the type or dosage of any prophylactic medications for indications other than chronic migraine that in the opinion of the clinician may interfere with the study
Exclusion criteria
* Has a history of aneurysm, intracranial hemorrhage, brain tumors or significant head trauma. * Has a lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the GammaCore treatment site. * 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. * 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) * Has had a previous bilateral, right, or left cervical vagotomy. * Has uncontrolled high blood pressure. * 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. * Has a history of carotid endarterectomy or vascular neck surgery on the right side. * Has been implanted with metal cervical spine hardware or has a metallic implant near the GammaCore stimulation site. * Has a recent or repeated history of syncope. * Has a recent or repeated history of seizure. * Has a known history or suspicion of substance abuse or addiction. * Has had a surgery for migraine prevention. * Has received Botox injections for migraine prevention within the past 6 months. * Has taken medications for migraine prophylaxis in the previous 30 days. * 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. * 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. * Is participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days. * Belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with follow-up requirements, or provide self-assessments is compromised (e.g., homeless, developmentally disabled, prisoner). * Is a relative of or an employee of the investigator or the clinical study site.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Number of Participants With Adverse Events | Up to 8 weeks - duration of the Randomized period | Safety was assessed by collecting Adverse Effects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Headache Days | Run-in period (4 weeks no treatment) and Randomized period (8 weeks) | Mean change in headache days. Change between 4 week run in period to the 8 weeks randomized period. |
| Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Run-in (4 weeks no treatment) and Randomized (8 weeks) | Peak severity per headache day was reported each headache day in the subject diary. Pain was reported as mild, moderate or severe. Whereas as mild = least severe and severe = most severe. |
| Use of Pain Relief Medication | Randomized period - 8 weeks | All abortive headache medication taken during randomized period |
| Mean Change in Quality of Life Short Form Survey (SF-12) | Run-in (4 weeks) and Randomized period (8 weeks) | The Quality of Life Short Form Survey (SF-12) is a multipurpose short form survey with 12 questions that are combined, scored and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. The SF-12 is weighted and summed to provide easily interpretable scales for physical and mental health. Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of the twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. SF-12 were recorded in the subject diary at the Phase 1 follow-up visit (week 4) and during Phase 2 randomized period at week 4 and week 8. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GammaCore Active Device Subjects will use an Active GammaCore Device
GammaCore Active Device | 30 |
| GammaCore Sham Device Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study. | 29 |
| Total | 59 |
Baseline characteristics
| Characteristic | GammaCore Active Device | GammaCore Sham Device | Total |
|---|---|---|---|
| Age, Continuous | 39.7 years | 41.0 years | 40 years |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 26 Participants | 25 Participants | 51 Participants |
| Region of Enrollment United States | 30 Participants | 29 Participants | 59 Participants |
| Sex: Female, Male Female | 26 Participants | 27 Participants | 53 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 29 |
| other Total, other adverse events | 6 / 30 | 5 / 29 |
| serious Total, serious adverse events | 2 / 30 | 0 / 29 |
Outcome results
Primary
Safety - Number of Participants With Adverse Events
Safety was assessed by collecting Adverse Effects
Time frame: Up to 8 weeks - duration of the Randomized period
Population: Randomized population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GammaCore Active Device | Safety - Number of Participants With Adverse Events | 6 Participants |
| GammaCore Sham Device | Safety - Number of Participants With Adverse Events | 5 Participants |
Secondary
Mean Change in Headache Days
Mean change in headache days. Change between 4 week run in period to the 8 weeks randomized period.
Time frame: Run-in period (4 weeks no treatment) and Randomized period (8 weeks)
Population: Data missing for 1 subject in each treatment group
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GammaCore Active Device | Mean Change in Headache Days | -1.5 days | Standard Deviation 5.92 |
| GammaCore Sham Device | Mean Change in Headache Days | -0.2 days | Standard Deviation 3.52 |
Secondary
Mean Change in Quality of Life Short Form Survey (SF-12)
The Quality of Life Short Form Survey (SF-12) is a multipurpose short form survey with 12 questions that are combined, scored and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. The SF-12 is weighted and summed to provide easily interpretable scales for physical and mental health. Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of the twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. SF-12 were recorded in the subject diary at the Phase 1 follow-up visit (week 4) and during Phase 2 randomized period at week 4 and week 8.
Time frame: Run-in (4 weeks) and Randomized period (8 weeks)
Population: Randomized period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GammaCore Active Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Run-in PCS score | 40.9 Score on a scale | Standard Deviation 9.62 |
| GammaCore Active Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Randomized period PCS score 4 weeks | 44.0 Score on a scale | Standard Deviation 9.25 |
| GammaCore Active Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Randomized period PCS scores 8 weeks | 45.3 Score on a scale | Standard Deviation 8.01 |
| GammaCore Active Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Run-in MCS scores | 44.5 Score on a scale | Standard Deviation 11.41 |
| GammaCore Active Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Randomized period MCS scores 4 weeks | 44.7 Score on a scale | Standard Deviation 10.53 |
| GammaCore Active Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Randomized period MCS scores 8 weeks | 46.5 Score on a scale | Standard Deviation 9.95 |
| GammaCore Sham Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Randomized period MCS scores 4 weeks | 45.8 Score on a scale | Standard Deviation 11.71 |
| GammaCore Sham Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Run-in PCS score | 35.6 Score on a scale | Standard Deviation 10.46 |
| GammaCore Sham Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Run-in MCS scores | 45.8 Score on a scale | Standard Deviation 10.55 |
| GammaCore Sham Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Randomized period PCS score 4 weeks | 37.5 Score on a scale | Standard Deviation 12.73 |
| GammaCore Sham Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Randomized period MCS scores 8 weeks | 44.3 Score on a scale | Standard Deviation 12.24 |
| GammaCore Sham Device | Mean Change in Quality of Life Short Form Survey (SF-12) | Randomized period PCS scores 8 weeks | 38.0 Score on a scale | Standard Deviation 10.67 |
Secondary
Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe
Peak severity per headache day was reported each headache day in the subject diary. Pain was reported as mild, moderate or severe. Whereas as mild = least severe and severe = most severe.
Time frame: Run-in (4 weeks no treatment) and Randomized (8 weeks)
Population: Randomized population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GammaCore Active Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Run-in Mild | 167 Headache days |
| GammaCore Active Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Run-in Moderate | 297 Headache days |
| GammaCore Active Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Run-in Severe | 190 Headache days |
| GammaCore Active Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Randomized Mild | 297 Headache days |
| GammaCore Active Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Randomized Moderate | 443 Headache days |
| GammaCore Active Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Randomized Severe | 274 Headache days |
| GammaCore Sham Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Randomized Moderate | 511 Headache days |
| GammaCore Sham Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Run-in Mild | 131 Headache days |
| GammaCore Sham Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Randomized Mild | 250 Headache days |
| GammaCore Sham Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Run-in Moderate | 330 Headache days |
| GammaCore Sham Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Randomized Severe | 395 Headache days |
| GammaCore Sham Device | Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe | Run-in Severe | 225 Headache days |
Secondary
Use of Pain Relief Medication
All abortive headache medication taken during randomized period
Time frame: Randomized period - 8 weeks
Population: Randomized population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GammaCore Active Device | Use of Pain Relief Medication | Subjects taking abortive medication | 26 Participants |
| GammaCore Active Device | Use of Pain Relief Medication | Subjects taking no abortive medication | 3 Participants |
| GammaCore Active Device | Use of Pain Relief Medication | Subjects with no data | 1 Participants |
| GammaCore Sham Device | Use of Pain Relief Medication | Subjects with no data | 1 Participants |
| GammaCore Sham Device | Use of Pain Relief Medication | Subjects taking abortive medication | 25 Participants |
| GammaCore Sham Device | Use of Pain Relief Medication | Subjects taking no abortive medication | 3 Participants |