Trial Outcomes & Findings for A Non-Invasive Neuromodulation Device for Treatment of Migraine Headache (NCT NCT01899040)

NCT ID: NCT01899040

Last Updated: 2025-05-31

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 100 participants
• Primary outcome timeframe: after 84 days of Device use
• Results posted on: 2025-05-31

Participant Flow

Participant milestones

Measure	Active Device A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	Placebo Device (Inactive Device) A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	Placebo Device (Partially Active) 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.
Overall Study STARTED	50	30	20
Overall Study COMPLETED	42	22	17
Overall Study NOT COMPLETED	8	8	3

Reasons for withdrawal

Measure	Active Device A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	Placebo Device (Inactive Device) A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	Placebo Device (Partially Active) 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.
Overall Study Randomized in error	0	1	1
Overall Study Adverse Event	3	1	2
Overall Study Unspecified reasons	4	4	0
Overall Study Compliance issues	1	2	0

Baseline Characteristics

Only participants that had data for this baseline measure were included in the analysis. Two (2) inactive placebo participants did not have baseline population for this baseline measure.

Baseline characteristics by cohort

Measure	BID Active n=50 Participants 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.	BID Inactive Placebo n=30 Participants 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.	BID Partially-Active Placebo n=20 Participants 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.	Total n=100 Participants Total of all reporting groups
Age, Continuous	44.0 Years STANDARD_DEVIATION 11.1 • n=50 Participants • Only participants that had data for this baseline measure were included in the analysis. Two (2) inactive placebo participants did not have baseline population for this baseline measure.	40.7 Years STANDARD_DEVIATION 12.4 • n=28 Participants • Only participants that had data for this baseline measure were included in the analysis. Two (2) inactive placebo participants did not have baseline population for this baseline measure.	42.3 Years STANDARD_DEVIATION 8.6 • n=20 Participants • Only participants that had data for this baseline measure were included in the analysis. Two (2) inactive placebo participants did not have baseline population for this baseline measure.	42.7 Years STANDARD_DEVIATION 11.0 • n=98 Participants • Only participants that had data for this baseline measure were included in the analysis. Two (2) inactive placebo participants did not have baseline population for this baseline measure.
Sex: Female, Male Female	44 Participants n=50 Participants	28 Participants n=30 Participants	17 Participants n=20 Participants	89 Participants n=100 Participants
Sex: Female, Male Male	6 Participants n=50 Participants	2 Participants n=30 Participants	3 Participants n=20 Participants	11 Participants n=100 Participants
Disease Duration	24.5 Years STANDARD_DEVIATION 12.4 • n=48 Participants • Only participants with data for this baseline analysis measure were included in this analysis. Disease duration was not collected for two(2) BID Active, one (1) BID Placebo, and three (3) BID Partially-Active Placebo participants.	20.8 Years STANDARD_DEVIATION 10.5 • n=29 Participants • Only participants with data for this baseline analysis measure were included in this analysis. Disease duration was not collected for two(2) BID Active, one (1) BID Placebo, and three (3) BID Partially-Active Placebo participants.	17.6 Years STANDARD_DEVIATION 8.4 • n=17 Participants • Only participants with data for this baseline analysis measure were included in this analysis. Disease duration was not collected for two(2) BID Active, one (1) BID Placebo, and three (3) BID Partially-Active Placebo participants.	22.1 Years STANDARD_DEVIATION 11.4 • n=94 Participants • Only participants with data for this baseline analysis measure were included in this analysis. Disease duration was not collected for two(2) BID Active, one (1) BID Placebo, and three (3) BID Partially-Active Placebo participants.
Years of Education	16.2 Years STANDARD_DEVIATION 2.6 • n=46 Participants • Only participants with data reported for this baseline measure are included in the analysis. Education data was not collected for four (4) BID Active and three (3) BID Placebo participants.	16.2 Years STANDARD_DEVIATION 2.6 • n=27 Participants • Only participants with data reported for this baseline measure are included in the analysis. Education data was not collected for four (4) BID Active and three (3) BID Placebo participants.	15.3 Years STANDARD_DEVIATION 2.5 • n=20 Participants • Only participants with data reported for this baseline measure are included in the analysis. Education data was not collected for four (4) BID Active and three (3) BID Placebo participants.	16.0 Years STANDARD_DEVIATION 2.6 • n=93 Participants • Only participants with data reported for this baseline measure are included in the analysis. Education data was not collected for four (4) BID Active and three (3) BID Placebo participants.
Baseline migraine days	7.7 days STANDARD_DEVIATION 2.5 • n=39 Participants • Only participants with data reported for this baseline measure are included in the analysis. Data is missing for this baseline measure due to the original headache diaries being either inaccessible or not completed by the participants at the time of the study.	6.9 days STANDARD_DEVIATION 2.9 • n=19 Participants • Only participants with data reported for this baseline measure are included in the analysis. Data is missing for this baseline measure due to the original headache diaries being either inaccessible or not completed by the participants at the time of the study.	8.3 days STANDARD_DEVIATION 2.5 • n=16 Participants • Only participants with data reported for this baseline measure are included in the analysis. Data is missing for this baseline measure due to the original headache diaries being either inaccessible or not completed by the participants at the time of the study.	7.6 days STANDARD_DEVIATION 2.6 • n=74 Participants • Only participants with data reported for this baseline measure are included in the analysis. Data is missing for this baseline measure due to the original headache diaries being either inaccessible or not completed by the participants at the time of the study.

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	BID Active Device n=38 Participants A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	BID Placebo (Fully Inactive Device) n=19 Participants A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	BID Placebo (Partially Active) A standardized, partially-active placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.
Change in Number of Monthly Migraine Headache Days	-3.5 migraine days Standard Deviation 0.6	-1.1 migraine days Standard Deviation 0.6	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	BID Active Device n=38 Participants A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	BID Placebo (Fully Inactive Device) n=19 Participants A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	BID Placebo (Partially Active) A standardized, partially-active placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.
Number of Monthly Migraine Headache Days (Reduction by by 50% or More)	20 Participants	6 Participants	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	BID Active Device n=38 Participants A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	BID Placebo (Fully Inactive Device) n=19 Participants A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	BID Placebo (Partially Active) A standardized, partially-active placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.
Total Monthly Headache Pain Score	-19.3 score on a scale Standard Deviation 3.6	-10.3 score on a scale Standard Deviation 3.4	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	BID Active Device n=40 Participants A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	BID Placebo (Fully Inactive Device) n=22 Participants A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	BID Placebo (Partially Active) n=17 Participants A standardized, partially-active placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.
(Safety Measure) Mood and Cognition - Change in Beck Depression Index Score	-0.7 score on a scale Standard Deviation 0.4	-0.9 score on a scale Standard Deviation 0.7	-0.9 score on a scale Standard Deviation 1.4

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	BID Active Device n=42 Participants A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	BID Placebo (Fully Inactive Device) n=22 Participants A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	BID Placebo (Partially Active) n=17 Participants A standardized, partially-active placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.
(Safety Measure) Dizziness: Verify the Absence of Change in Material Dizziness (Berg Balance)	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0	0.3 score on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	BID Active Device n=40 Participants A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	BID Placebo (Fully Inactive Device) n=22 Participants A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	BID Placebo (Partially Active) n=17 Participants A standardized, partially-active placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.
(Safety Measure) Mood and Cognition - Change in Digit Symbol Coding Cognitive Speed	7.1 tasks completed Standard Deviation 1.9	5.0 tasks completed Standard Deviation 1.9	7.4 tasks completed Standard Deviation 2.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	BID Active Device n=40 Participants A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	BID Placebo (Fully Inactive Device) n=22 Participants A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	BID Placebo (Partially Active) n=17 Participants A standardized, partially-active placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.
(Safety Measure) Mood and Cognition Measure - Change in Short Term Memory Test Scores	-1.0 score on a scale Standard Deviation 1.0	-1.9 score on a scale Standard Deviation 1.5	1.0 score on a scale Standard Deviation 1.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	BID Active Device n=38 Participants A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	BID Placebo (Fully Inactive Device) n=19 Participants A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	BID Placebo (Partially Active) A standardized, partially-active placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.
Average of Monthly Treated Headaches (Acute Anti-migraine Prescription Drug Intake)	-3.5 # acute antimigraine medication intakes Standard Deviation 0.6	-1.8 # acute antimigraine medication intakes Standard Deviation 0.8	—

Adverse Events

Active Device

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo Device (Fully-inactive Device)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo Device (Partially Active Device)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Active Device n=50 participants at risk A standardized, active tvCVS neuromodulation waveform treatment delivered by a device used twice daily for all active Device patients at all Study sites.	Placebo Device (Fully-inactive Device) n=30 participants at risk A standardized, fully-inactive placebo tvCVS neuromodulation waveform treatment delivered twice daily by the study device was used for this group at all Study sites.	Placebo Device (Partially Active Device) n=20 participants at risk 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 only safety (adverse events and safety outcome measures) for the duration of the study.
Infections and infestations Bronchitis	6.0% 3/50 • Number of events 3 • 12 weeks clinicaltrials.gov terms were used.	6.7% 2/30 • Number of events 2 • 12 weeks clinicaltrials.gov terms were used.	0.00% 0/20 • 12 weeks clinicaltrials.gov terms were used.
Infections and infestations Sinus Infection	8.0% 4/50 • Number of events 4 • 12 weeks clinicaltrials.gov terms were used.	0.00% 0/30 • 12 weeks clinicaltrials.gov terms were used.	0.00% 0/20 • 12 weeks clinicaltrials.gov terms were used.
Nervous system disorders Migraine	6.0% 3/50 • Number of events 5 • 12 weeks clinicaltrials.gov terms were used.	0.00% 0/30 • 12 weeks clinicaltrials.gov terms were used.	5.0% 1/20 • Number of events 1 • 12 weeks clinicaltrials.gov terms were used.
Gastrointestinal disorders Nausea	6.0% 3/50 • Number of events 3 • 12 weeks clinicaltrials.gov terms were used.	6.7% 2/30 • Number of events 2 • 12 weeks clinicaltrials.gov terms were used.	15.0% 3/20 • Number of events 3 • 12 weeks clinicaltrials.gov terms were used.
Infections and infestations Cold	10.0% 5/50 • Number of events 5 • 12 weeks clinicaltrials.gov terms were used.	10.0% 3/30 • Number of events 3 • 12 weeks clinicaltrials.gov terms were used.	5.0% 1/20 • Number of events 1 • 12 weeks clinicaltrials.gov terms were used.

Additional Information

Robert Black

Scion NeuroStim, Inc

Phone: 919-260-5528

Email: bacllc@earthlink.net

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place