Acute Migraine
Conditions
Brief summary
this study will evaluate the clinical performance and safety of a self administered abortive treatment for migraine headache using combined occipital and supraorbital transcutaneous nerve stimulator (Neurolief device, Relivion®)
Detailed description
The Relivion® is a non-invasive transcutaneous neuro-stimulator is indicated for the acute treatment of migraine with or without aura in subjects 18 years of age or older. The Relivion® is intended to be a prescription device, self-used at home.
Interventions
DEVICERelivion active
1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation
DEVICERelivion Sham
1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation
Sponsors
Neurolief Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects 18 years of age and older. 2. Subject meets the ICHD (International Classification of Headache Disorders)-3 (2018) diagnostic criteria for Migraine with or without aura. 3. Subject reports 1-6 Migraine attacks per month; other headaches no more than 6 days per month. 4. Subject is willing to and capable of complying with the specified study requirements, provided written Informed Consent, can complete the electronic diaries, and can be contacted by telephone.
Exclusion criteria
1. Subject having received Botox treatment in the head region in the prior 3 months. 2. Subject having received supraorbital or occipital nerve blocks in the prior month. 3. Past 6 months of chronic migraine, New Daily Persistent Headache, and chronic tension-type headache per ICHD-3 (2018) diagnostic criteria. 4. Current medication overuse headache. 5. Use of opioid medications in the prior 1 month. 6. Use of barbiturates in the prior 1 month. 7. Subject has \>10 headache days per month 8. Implanted metal/shrapnel or electrical devices in the head (not including dental implants), a cardiac pacemaker or an implanted or wearable defibrillator. 9. Received parenteral infusions for migraine within the previous 2 weeks. 10. Subject has known uncontrolled epilepsy. 11. History of neurosurgical interventions 12. Subject with implanted neurostimulators, surgical clips (above the shoulder line) or any medical pumps. 13. Current drug abuse or alcoholism. 14. Subject is participating in any other clinical study. 15. Skin lesion or inflammation at the region of the stimulating electrodes. 16. Personality or somatoform disorder. 17. Pregnancy or Lactation. 18. Women with child bearing potential without medically acceptable method of contraception (NOTE: Females of child bearing potential must have a negative pregnancy test). 19. Documented history of cerebrovascular event. 20. Subject with recent brain or facial trauma (occurred less than 3 months prior to this study). 21. Subject participated in a previous study with the Relivion device. 22. The subject does not have the basic cognitive and motor skills needed to operate a smartphone. 23. Subject with head circumference smaller than 51 centimeters or head circumference larger than 60 centimeters 24. Subject with other significant pain problem that in the opinion of the investigator may confound the study assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Reporting Reduction of Migraine Headache Pain at 2 Hours From Treatment Initiation | 2 hours from treatment initiation | the number and percent of subjects reporting reduction of migraine headache pain 2 hours post treatment initiation from severe or moderate to mild or no pain, or from mild to no pain, in their first eligible treated migraine attack (if rescue therapy was not used) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Reporting Improvement in Their Most Bothersome Symptom (MBS) Other Than a Headache, 2 Hours Post-treatment Initiation | 2 hours from treatment initiation | The number and percentage of subjects reporting improvement in their Most Bothersome Symptom (MBS) other than a headache, 2 hours post-treatment initiation (if rescue therapy was not used), in their first eligible treated migraine attack. MBS may be nausea, photophobia, phonophobia |
| Proportion of Subjects Reporting Reduction of Migraine Headache Pain 1-hour Post Treatment Initiation | 1 hour from treatment initiation | The number and percentage of subjects reporting reduction of migraine headache pain 1-hour post treatment initiation (if rescue therapy was not used), from severe or moderate to mild or no pain, or from mild to no pain, in their first eligible treated migraine attack |
| Proportion of Subjects Who Are Pain Free at 2 Hours Post Treatment Initiation | 2 hours from treatment initiation | The number and percentage of subjects who are pain free at 2 hours post treatment initiation (if rescue therapy was not used), in their first eligible treated migraine attack |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From Enrollment (randomization) through study exit i.e. 70 days | Safety of the study device following study treatment: Number and Rate of participates with Adverse events related or unrelated to the study device |
| The Change in Pseudo-continuous Pain Score From Baseline to 1-hour Post Treatment | baseline to 1-hour post treatment | as per the Statistical Considerations for Clinical Trials During the COVID-19 Public Health Emergency June 2020 FDA Guidance, which states that a modifications to the definition and ascertainment of trial endpoints may be warranted to address the impact of COVID-19. A potential modification for a binary endpoint that is based on a continuous or ordinal measurement is by using the continuous or ordinal measurement as the endpoint. therefore, an additional analysis to the study end points , the migraine headache pain level was transformed into a numerical score (pseudo-continuous): No pain=0, Mild=1, Moderate=2, Severe=3. If rescue medication was used, the score after the rescue intake post-treatment are set to the baseline value. The change from baseline is compared between the study arms with an analysis of covariance model adjusted for site and baseline pain level. |
Countries
Israel, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Relivion Active device
Relivion active: 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation | 67 |
| Sham Relivion Sham device
Relivion Sham: 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation | 64 |
| Total | 131 |
Baseline characteristics
| Characteristic | Sham | Total | Active |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 64 Participants | 130 Participants | 66 Participants |
| Age, Continuous | 39.9 years STANDARD_DEVIATION 13.03 | 40.3 years STANDARD_DEVIATION 12.7 | 40.7 years STANDARD_DEVIATION 12.47 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 57 Participants | 117 Participants | 60 Participants |
| Region of Enrollment Israel | 40 participants | 78 participants | 38 participants |
| Region of Enrollment United States | 24 participants | 53 participants | 29 participants |
| Sex: Female, Male Female | 51 Participants | 109 Participants | 58 Participants |
| Sex: Female, Male Male | 13 Participants | 22 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 64 |
| other Total, other adverse events | 8 / 67 | 2 / 64 |
| serious Total, serious adverse events | 0 / 67 | 0 / 64 |
Outcome results
Primary
Proportion of Subjects Reporting Reduction of Migraine Headache Pain at 2 Hours From Treatment Initiation
the number and percent of subjects reporting reduction of migraine headache pain 2 hours post treatment initiation from severe or moderate to mild or no pain, or from mild to no pain, in their first eligible treated migraine attack (if rescue therapy was not used)
Time frame: 2 hours from treatment initiation
Population: mITT present the number and percentage of subjects with pain relief (reduction in pain level) 2 hours post-treatment, from severe or moderate to mild or no pain, or from mild to no pain, in their first eligible treated episode. If a subject had used rescue medication up to the assessment time point, he/she was considered as not reaching the endpoint. mITT set included 50 patients in the Active arm and 59 patients in the sham arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Proportion of Subjects Reporting Reduction of Migraine Headache Pain at 2 Hours From Treatment Initiation | 30 Participants |
| Sham | Proportion of Subjects Reporting Reduction of Migraine Headache Pain at 2 Hours From Treatment Initiation | 22 Participants |
p-value: 0.018Chi-squared
Secondary
Proportion of Subjects Reporting Improvement in Their Most Bothersome Symptom (MBS) Other Than a Headache, 2 Hours Post-treatment Initiation
The number and percentage of subjects reporting improvement in their Most Bothersome Symptom (MBS) other than a headache, 2 hours post-treatment initiation (if rescue therapy was not used), in their first eligible treated migraine attack. MBS may be nausea, photophobia, phonophobia
Time frame: 2 hours from treatment initiation
Population: mITT population analysis. mITT set included 50 patients in the Active arm from which 36 reported MBS and 59 patients in the sham arm from which 45 reported MBS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Proportion of Subjects Reporting Improvement in Their Most Bothersome Symptom (MBS) Other Than a Headache, 2 Hours Post-treatment Initiation | 29 Participants |
| Sham | Proportion of Subjects Reporting Improvement in Their Most Bothersome Symptom (MBS) Other Than a Headache, 2 Hours Post-treatment Initiation | 27 Participants |
p-value: 0.0466Chi-squared
Secondary
Proportion of Subjects Reporting Reduction of Migraine Headache Pain 1-hour Post Treatment Initiation
The number and percentage of subjects reporting reduction of migraine headache pain 1-hour post treatment initiation (if rescue therapy was not used), from severe or moderate to mild or no pain, or from mild to no pain, in their first eligible treated migraine attack
Time frame: 1 hour from treatment initiation
Population: mITT population analysis. mITT set included 50 patients in the Active arm and 59 patients in the sham arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Proportion of Subjects Reporting Reduction of Migraine Headache Pain 1-hour Post Treatment Initiation | 21 Participants |
| Sham | Proportion of Subjects Reporting Reduction of Migraine Headache Pain 1-hour Post Treatment Initiation | 15 Participants |
p-value: 0.0677Chi-squared
Secondary
Proportion of Subjects Who Are Pain Free at 2 Hours Post Treatment Initiation
The number and percentage of subjects who are pain free at 2 hours post treatment initiation (if rescue therapy was not used), in their first eligible treated migraine attack
Time frame: 2 hours from treatment initiation
Population: mITT population anaylsis. mITT set included 50 patients in the Active arm and 59 patients in the sham arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Proportion of Subjects Who Are Pain Free at 2 Hours Post Treatment Initiation | 23 Participants |
| Sham | Proportion of Subjects Who Are Pain Free at 2 Hours Post Treatment Initiation | 7 Participants |
p-value: <0.0001Chi-squared
Other Pre-specified
Number of Participants With Adverse Events
Safety of the study device following study treatment: Number and Rate of participates with Adverse events related or unrelated to the study device
Time frame: From Enrollment (randomization) through study exit i.e. 70 days
Population: ITT population analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active | Number of Participants With Adverse Events | Participants with Adverse Events | 8 Participants |
| Active | Number of Participants With Adverse Events | Participants with device related Adverse Events | 5 Participants |
| Sham | Number of Participants With Adverse Events | Participants with Adverse Events | 2 Participants |
| Sham | Number of Participants With Adverse Events | Participants with device related Adverse Events | 2 Participants |
p-value: 0.0968Fisher Exact
Other Pre-specified
The Change in Pseudo-continuous Pain Score From Baseline to 1-hour Post Treatment
as per the Statistical Considerations for Clinical Trials During the COVID-19 Public Health Emergency June 2020 FDA Guidance, which states that a modifications to the definition and ascertainment of trial endpoints may be warranted to address the impact of COVID-19. A potential modification for a binary endpoint that is based on a continuous or ordinal measurement is by using the continuous or ordinal measurement as the endpoint. therefore, an additional analysis to the study end points , the migraine headache pain level was transformed into a numerical score (pseudo-continuous): No pain=0, Mild=1, Moderate=2, Severe=3. If rescue medication was used, the score after the rescue intake post-treatment are set to the baseline value. The change from baseline is compared between the study arms with an analysis of covariance model adjusted for site and baseline pain level.
Time frame: baseline to 1-hour post treatment
Population: mITT set included 50 patients in the Active arm and 59 patients in the sham arm
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active | The Change in Pseudo-continuous Pain Score From Baseline to 1-hour Post Treatment | -0.637 units on a scale |
| Sham | The Change in Pseudo-continuous Pain Score From Baseline to 1-hour Post Treatment | -0.306 units on a scale |
p-value: 0.0121ANCOVA