Migraine Headache, Episodic
Conditions
Keywords
neuromodulation, migraine headache, CVS
Brief summary
This is a randomized, blinded study designed to assess the efficacy of a portable, non-invasive neuromodulation system for the treatment of episodic migraine headaches.
Detailed description
This is a multi-center, triple-blinded, placebo-controlled, randomized pivotal trial evaluating the adjunctive prophylactic treatment of episodic migraine headache using a caloric vestibular stimulation (CVS) device developed by Scion NeuroStim, LLC (SNS). This study has been reviewed by the FDA and is categorized as posing NSR (nonsignificant risk).
Interventions
DEVICEneuromodulation for episodic migraine headache
Sponsors
Scion NeuroStim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
The study was designed with two arms - active and placebo. The devices for the first 20 placebo-randomized participants were found to be partially active. Therefore, the fully placebo arm was separated into placebo and partially active placebo. Only the active and placebo arms were followed (and outcomes posted) for effectiveness. All (active, placebo, and partially active) were followed and outcomes posted for safety.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* The patient must have been diagnosed with episodic Migraine Headache at least 6 months prior to entering into the Study, consistent with the International Headache Classification of Headache Disorders-II (ICHD-II) guidelines. * The patient must have a history of at least three consecutive months of stable Migraine Headaches prior to entering the Study. The patients will not have had changes in medication usage for the three Months leading up to the Study, nor will they introduce new medications during the Study period. Patients will satisfy these criteria: On a Monthly basis, at least four, and not more than a total of fourteen (4-14), Headache Days (Pain Score between one and ten) of which between four and nine (4-14) are Migraine Headache Days * The patient must not have failed on more than two classes of properly administered prophylactic pharmaceutical therapies for migraine headache. The patient may be on a single migraine prophylactic as long as the dosage has not been altered within 3 months of starting the study and the dosage must not be altered for the duration of the study. * The Investigator must have confidence in the patient's ability to reliably use the Experimental Device and promptly complete the Daily Headache Diary forms. The Daily Headache Diary will be completed from the beginning of the Pre-Treatment Baseline Period through the end of the Pivotal Study.
Exclusion criteria
Individuals who: * are pregnant * have a history of cardiovascular disease * work night shifts * have been diagnosed with vestibular migraine * have been diagnosed with migraine with aura * have menstrual migraine exclusively * have been diagnosed with post-traumatic migraine * have a history of unstable mood disorder or unstable anxiety disorder * use a hearing aid * have a cochlear implant * have chronic tinnitus * have temporomandibular joint (TMJ) disease * have been diagnosed with traumatic brain injury (TBI) * have been diagnosed with neurological disease other than Headaches * have a diagnosed vestibular dysfunction * abuse alcohol or other drugs * are experiencing medication overuse Headaches (individuals with respect to whom the Investigator is concerned that analgesic abuse is involved based on the ICHD-II guidelines). * are younger than 18 years or older than 65 years * have had eye surgery within the previous three months or ear surgery within the previous six months * have active ear infections or a perforated tympanic membrane * have participated in another clinical trial within the last 30 days or are currently enrolled in another clinical trial * are using Botox treatments for migraines * Though not excluded, patients taking anti-histamines or anti-nausea drugs will be encouraged not to take such medications within four hours prior to using the Device. The Investigator should review other medications taken by the patient with properties that mimic anti-nausea or anti-dizziness drugs as these may reduce responsiveness to stimulation. Such medications should also be avoided within four hours prior to a treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Monthly Migraine Headache Days | after 84 days of Device use | Change in the average total number of Monthly Migraine Headache Days (number of days in the month that a participant experienced a migraine) after 3 months of treatment comparable to the pre-device use Baseline Period of 1 month, as reported in a headache diary. Negative number indicated improvement (a reduction in the average number of migraine headache days experienced per month). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Monthly Migraine Headache Days (Reduction by by 50% or More) | after 84 days of Device use | Number of participants that experienced a reduction of 50% or more in Monthly Migraine Headache Days (total days during a month on which a migraine occurred) during the third month of device use as compared with their pre-device use Baseline Period. |
| Total Monthly Headache Pain Score | after 84 days of Device use | After three months of Device use, the average Total Monthly Headache Pain Score compared to the average derived from the Pre-use Baseline Period (1 month). This is calculated by adding the cumulative maximum pain scores for all days the subject had a headache, as noted as the maximum daily headache pain score on a scale of 1 (lowest pain)-10 (highest pain) for each headache day as reported by the subject in their daily headache diary. Each month was counted as 28 days. Therefore, the total possible score for each month was 28-280. A negative number indicates a reduction in pain score. |
| (Safety Measure) Dizziness: Verify the Absence of Change in Material Dizziness (Berg Balance) | after 84 days of Device use | The purpose of this study endpoint is to verify, using the Berg Balance test, the absence of change in material dizziness (with the associated risk of falls) as a consequence of using the Device. The test consists of 14 balance- related tasks ranging from standing up from a sitting position to standing on one foot. Each task is graded from 0 - 4, and the final measure is the sum from all elements of the Test: • 41-56 = low risk of fall • 21-40 = medium risk of fall • 0-20 = high risk of fall. Possible scores range from 0-56. Scores of zero indicate no change in balance. |
| (Safety Measure) Mood and Cognition - Change in Beck Depression Index Score | after 84 days of Device use | A patient's Pre-device use Baseline Period mood score from the Beck Depression Index is compared with those at the end of the 3 month Device use period. The Beck Depression Inventory (BDI) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression, with each of the 21 items, rated on a 4-point scale (0-3). The total scores rage from 0-63. The higher the score the more depressed. Mood scores are assessed for: decline, no change, or an improvement. A negative score indicates improvement in mood. |
| (Safety Measure) Mood and Cognition Measure - Change in Short Term Memory Test Scores | after 84 days of Device use | A patient's Pre-use Baseline Period memory scores, using Short Term memory test (an old/new paradigm for face recognition) are compared with those at the end of the 3-month Device use period. This assessment was created by the study Neuropsychologist where participants were shown faces at baseline then shown another set which included a subset then had seen before and had to say if they had seen them before later during the visit (to test short term memory). Scores range from 0-10. Higher scores indicate better short term memory. Memory scores were assessed for: a decline, no change, or an improvement from baseline to the end of treatment month 3. A negative score indicates improvement. |
| Average of Monthly Treated Headaches (Acute Anti-migraine Prescription Drug Intake) | after 84 days of device use | This measures counts the number of times abortive medications are taken. The baseline count is subtracted from the third month count. A negative number indicates a reduction in abortive medications used. The greater the negative number, the more reduced the use of abortive medications. |
| (Safety Measure) Mood and Cognition - Change in Digit Symbol Coding Cognitive Speed | after 84 days of Device use | A patient's Pre-use Baseline Period cognitive speed scores, using the Digit Symbol Coding assessment, will be compared with those at the end of the Device use period. The Digit-Symbol Subtest of the WAIS-III, is a timed pencil-and-paper task that measures processing speed and visual-motor coordination. It involves matching symbols to numbers using a key, with the goal of completing as many correct matches as possible within a 120-second time limit. The number of correct matches completed is counted. The lowest possible count is 0 (zero correct matches). The higher the number of correct matches completed, the better the cognitive speed of the participant. Cognitive speed will be assessed for: a decline, no change, or an improvement. A positive number indicates improvement. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BID Active Participants (episodic migraineurs) self-administered twice-daily active treatments for 12 weeks
The Device delivered a standardized, active tvCVS neuromodulation waveform twice-daily to all active Device patients at all Study sites. | 50 |
| BID Inactive Placebo Participants (episodic migraineurs) self-administered twice-daily inactive/sham treatments for 12 weeks
The Device delivered a standardized, placebo (no power to the earpieces) tvCVS neuromodulation waveform twice-daily to all inactive placebo Device patients at all Study sites. | 30 |
| BID Partially-Active Placebo Participants (episodic migraineurs) self-administered twice-daily partially active treatments for 12 weeks
The description of this treatment is a standardized partially-active neuromodulation waveform delivered twice daily was used for the first 20 participants randomized to the placebo group at all Study sites.
While the participants in this group were supposed to have received a fully-inactive waveform, their devices were found to be delivering an unintended partially-active treatment. This was discovered well after the study had begun. As their results did not represent use of a true (i.e., fully inactive) device, these participants were separated from the main placebo group and followed for safety only for the duration of the study. | 20 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 2 |
| Overall Study | Compliance issues | 1 | 2 | 0 |
| Overall Study | Randomized in error | 0 | 1 | 1 |
| Overall Study | Unspecified reasons | 4 | 4 | 0 |
Baseline characteristics
| Characteristic | BID Active | BID Inactive Placebo | BID Partially-Active Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 44.0 Years STANDARD_DEVIATION 11.1 | 40.7 Years STANDARD_DEVIATION 12.4 | 42.3 Years STANDARD_DEVIATION 8.6 | 42.7 Years STANDARD_DEVIATION 11 |
| Baseline migraine days | 7.7 days STANDARD_DEVIATION 2.5 | 6.9 days STANDARD_DEVIATION 2.9 | 8.3 days STANDARD_DEVIATION 2.5 | 7.6 days STANDARD_DEVIATION 2.6 |
| Disease Duration | 24.5 Years STANDARD_DEVIATION 12.4 | 20.8 Years STANDARD_DEVIATION 10.5 | 17.6 Years STANDARD_DEVIATION 8.4 | 22.1 Years STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 44 Participants | 28 Participants | 17 Participants | 89 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 3 Participants | 11 Participants |
| Years of Education | 16.2 Years STANDARD_DEVIATION 2.6 | 16.2 Years STANDARD_DEVIATION 2.6 | 15.3 Years STANDARD_DEVIATION 2.5 | 16.0 Years STANDARD_DEVIATION 2.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 30 | 0 / 20 |
| other Total, other adverse events | 14 / 50 | 7 / 30 | 5 / 20 |
| serious Total, serious adverse events | 0 / 50 | 0 / 30 | 0 / 20 |
Outcome results
Primary
Change in Number of Monthly Migraine Headache Days
Change in the average total number of Monthly Migraine Headache Days (number of days in the month that a participant experienced a migraine) after 3 months of treatment comparable to the pre-device use Baseline Period of 1 month, as reported in a headache diary. Negative number indicated improvement (a reduction in the average number of migraine headache days experienced per month).
Time frame: after 84 days of Device use
Population: Only participants who were confirmed to meet eligibility criteria, received either placebo (completely inactive) or fully active devices, and completed this outcome effectiveness measures were included in the overall number of participants analyzed for this outcome. Additional missing data comes from participants not being fully compliant with headache diary.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BID Active Device | Change in Number of Monthly Migraine Headache Days | -3.5 migraine days | Standard Deviation 0.6 |
| BID Placebo (Fully Inactive Device) | Change in Number of Monthly Migraine Headache Days | -1.1 migraine days | Standard Deviation 0.6 |
Secondary
Average of Monthly Treated Headaches (Acute Anti-migraine Prescription Drug Intake)
This measures counts the number of times abortive medications are taken. The baseline count is subtracted from the third month count. A negative number indicates a reduction in abortive medications used. The greater the negative number, the more reduced the use of abortive medications.
Time frame: after 84 days of device use
Population: Only participants who were confirmed to meet eligibility criteria and had baseline and month 3 data for this outcome were included in the overall number of participants analyzed for this outcome. As this is an effectiveness measure, only Active and Placebo (fully inactive) participants were followed and included in analysis. Additional missing data comes from participants not being fully compliant with headache diary.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BID Active Device | Average of Monthly Treated Headaches (Acute Anti-migraine Prescription Drug Intake) | -3.5 # acute antimigraine medication intakes | Standard Deviation 0.6 |
| BID Placebo (Fully Inactive Device) | Average of Monthly Treated Headaches (Acute Anti-migraine Prescription Drug Intake) | -1.8 # acute antimigraine medication intakes | Standard Deviation 0.8 |
Secondary
Number of Monthly Migraine Headache Days (Reduction by by 50% or More)
Number of participants that experienced a reduction of 50% or more in Monthly Migraine Headache Days (total days during a month on which a migraine occurred) during the third month of device use as compared with their pre-device use Baseline Period.
Time frame: after 84 days of Device use
Population: Only participants who were confirmed to meet eligibility criteria \& received either placebo (completely inactive) or fully active devices and completed primary and secondary outcome effectiveness measures were included in the overall number of participants analyzed for this outcome.~For both Active and Placebo, all participants with baseline and third month of data were included in analysis. Additional missing data comes from participants not being fully compliant with headache diary.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BID Active Device | Number of Monthly Migraine Headache Days (Reduction by by 50% or More) | 20 Participants |
| BID Placebo (Fully Inactive Device) | Number of Monthly Migraine Headache Days (Reduction by by 50% or More) | 6 Participants |
Secondary
(Safety Measure) Dizziness: Verify the Absence of Change in Material Dizziness (Berg Balance)
The purpose of this study endpoint is to verify, using the Berg Balance test, the absence of change in material dizziness (with the associated risk of falls) as a consequence of using the Device. The test consists of 14 balance- related tasks ranging from standing up from a sitting position to standing on one foot. Each task is graded from 0 - 4, and the final measure is the sum from all elements of the Test: • 41-56 = low risk of fall • 21-40 = medium risk of fall • 0-20 = high risk of fall. Possible scores range from 0-56. Scores of zero indicate no change in balance.
Time frame: after 84 days of Device use
Population: Only participants who were confirmed to meet eligibility criteria and completed this measure were included in the overall number of participants analyzed for this outcome. As this is a safety measure, active, placebo, and partially active groups were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BID Active Device | (Safety Measure) Dizziness: Verify the Absence of Change in Material Dizziness (Berg Balance) | 0.0 score on a scale | Standard Deviation 0 |
| BID Placebo (Fully Inactive Device) | (Safety Measure) Dizziness: Verify the Absence of Change in Material Dizziness (Berg Balance) | 0.0 score on a scale | Standard Deviation 0 |
| BID Placebo (Partially Active) | (Safety Measure) Dizziness: Verify the Absence of Change in Material Dizziness (Berg Balance) | 0.3 score on a scale | Standard Deviation 0.4 |
Secondary
(Safety Measure) Mood and Cognition - Change in Beck Depression Index Score
A patient's Pre-device use Baseline Period mood score from the Beck Depression Index is compared with those at the end of the 3 month Device use period. The Beck Depression Inventory (BDI) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression, with each of the 21 items, rated on a 4-point scale (0-3). The total scores rage from 0-63. The higher the score the more depressed. Mood scores are assessed for: decline, no change, or an improvement. A negative score indicates improvement in mood.
Time frame: after 84 days of Device use
Population: Only participants who were confirmed to meet eligibility criteria and completed baseline and month 3 for this measure were included in the overall number of participants analyzed for this outcome. As this is a safety measure, all (active, placebo, and partially active) participants were followed and outcomes presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BID Active Device | (Safety Measure) Mood and Cognition - Change in Beck Depression Index Score | -0.7 score on a scale | Standard Deviation 0.4 |
| BID Placebo (Fully Inactive Device) | (Safety Measure) Mood and Cognition - Change in Beck Depression Index Score | -0.9 score on a scale | Standard Deviation 0.7 |
| BID Placebo (Partially Active) | (Safety Measure) Mood and Cognition - Change in Beck Depression Index Score | -0.9 score on a scale | Standard Deviation 1.4 |
Secondary
(Safety Measure) Mood and Cognition - Change in Digit Symbol Coding Cognitive Speed
A patient's Pre-use Baseline Period cognitive speed scores, using the Digit Symbol Coding assessment, will be compared with those at the end of the Device use period. The Digit-Symbol Subtest of the WAIS-III, is a timed pencil-and-paper task that measures processing speed and visual-motor coordination. It involves matching symbols to numbers using a key, with the goal of completing as many correct matches as possible within a 120-second time limit. The number of correct matches completed is counted. The lowest possible count is 0 (zero correct matches). The higher the number of correct matches completed, the better the cognitive speed of the participant. Cognitive speed will be assessed for: a decline, no change, or an improvement. A positive number indicates improvement.
Time frame: after 84 days of Device use
Population: Only participants who were confirmed to meet eligibility criteria and completed this safety measure were included in the overall number of participants analyzed for this outcome. As this was a safety measure, active, placebo and partially active groups were followed and results presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BID Active Device | (Safety Measure) Mood and Cognition - Change in Digit Symbol Coding Cognitive Speed | 7.1 tasks completed | Standard Deviation 1.9 |
| BID Placebo (Fully Inactive Device) | (Safety Measure) Mood and Cognition - Change in Digit Symbol Coding Cognitive Speed | 5.0 tasks completed | Standard Deviation 1.9 |
| BID Placebo (Partially Active) | (Safety Measure) Mood and Cognition - Change in Digit Symbol Coding Cognitive Speed | 7.4 tasks completed | Standard Deviation 2.9 |
Secondary
(Safety Measure) Mood and Cognition Measure - Change in Short Term Memory Test Scores
A patient's Pre-use Baseline Period memory scores, using Short Term memory test (an old/new paradigm for face recognition) are compared with those at the end of the 3-month Device use period. This assessment was created by the study Neuropsychologist where participants were shown faces at baseline then shown another set which included a subset then had seen before and had to say if they had seen them before later during the visit (to test short term memory). Scores range from 0-10. Higher scores indicate better short term memory. Memory scores were assessed for: a decline, no change, or an improvement from baseline to the end of treatment month 3. A negative score indicates improvement.
Time frame: after 84 days of Device use
Population: Only participants who were confirmed to meet eligibility criteria and completed this outcome measure were included in the overall number of participants analyzed for this outcome. As this was a safety measure, all (active, placebo, and partially active) participants with baseline and third month of data were included in analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BID Active Device | (Safety Measure) Mood and Cognition Measure - Change in Short Term Memory Test Scores | -1.0 score on a scale | Standard Deviation 1 |
| BID Placebo (Fully Inactive Device) | (Safety Measure) Mood and Cognition Measure - Change in Short Term Memory Test Scores | -1.9 score on a scale | Standard Deviation 1.5 |
| BID Placebo (Partially Active) | (Safety Measure) Mood and Cognition Measure - Change in Short Term Memory Test Scores | 1.0 score on a scale | Standard Deviation 1.5 |
Secondary
Total Monthly Headache Pain Score
After three months of Device use, the average Total Monthly Headache Pain Score compared to the average derived from the Pre-use Baseline Period (1 month). This is calculated by adding the cumulative maximum pain scores for all days the subject had a headache, as noted as the maximum daily headache pain score on a scale of 1 (lowest pain)-10 (highest pain) for each headache day as reported by the subject in their daily headache diary. Each month was counted as 28 days. Therefore, the total possible score for each month was 28-280. A negative number indicates a reduction in pain score.
Time frame: after 84 days of Device use
Population: Only participants who were confirmed to meet eligibility criteria, received either active or placebo (completely inactive) treatments, and completed this effectiveness measure were included in the overall number of participants analyzed for this outcome.~Additional missing data comes from participants not being fully compliant with headache diary.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BID Active Device | Total Monthly Headache Pain Score | -19.3 score on a scale | Standard Deviation 3.6 |
| BID Placebo (Fully Inactive Device) | Total Monthly Headache Pain Score | -10.3 score on a scale | Standard Deviation 3.4 |