Chronic Migraine
Conditions
Brief summary
This study is intended to evaluate the efficacy and safety of Nerivio, an FDA-authorized remote electrical neuromodulation (REN) device for the acute treatment of migraine, for the acute treatment of migraine in people with chronic migraine. The device delivers transcutaneous electrical stimulation to the upper arm to induce conditioned pain modulation (CPM) that activates a descending endogenous analgesic mechanism. The study duration consists of a 4 weeks of active treatment with the device in about 40 patients.
Detailed description
This open label study includes up to 2 visits. The enrollment and device training may occur in 2 separate visits. First visit - The first visit will include screening, enrollment and training on the application and device. Treatment phase - Participants will be instructed to use the device for the treatment of qualifying migraine headaches (see below) as soon as possible and always within 60 minutes of onset during a period of up to 4 weeks. Participants will be instructed to use the device with the intensity level identified during the device training visit (and adjust as necessary) and make sure the stimulation is perceptible but not painful. Participants will be instructed to avoid taking rescue medications within 2 hours post-treatment. If medications are used, participants will be instructed to record in the app when and which medication was taken at 2- and 24-hours post treatment. The participants will use the app to record pain intensity levels, the presence/absence of aura and associated migraine symptoms (nausea, photophobia, phonophobia, and allodynia l) as well as rate their stress level and functional disability at baseline, 2- and 24-hours post-treatment. At the beginning of each treatment, participants will also be asked to report the time elapsed from attack onset. Adverse events will be reported throughout this phase of the study directly to the site staff. Participants who do not achieve satisfactory relief at 2 hours post-treatment may treat again with the Nerivio™ device or may treat with usual care at that time or any time thereafter if the headache does not resolve. Participants will also be able to treat headache recurrence with the device. Migraine headaches that are not treated with the device may be treated with usual care. The first reported treatment will be considered a training treatment, aimed to verify that the participants use the device properly, and will only be included in the safety analysis. The efficacy evaluation will be performed on the first treatment of a qualifying attack (see below) following the training treatment (hereby termed test treatment). Second (final) visit - End of study: Participants will return to the clinic following the end of the treatment phase, at which time they will return the device. The participants will have the option of returning the device by mail instead of an on-site visit.
Interventions
DEVICENerivio
The device delivers transcutaneous electrical stimulation to the upper arm to induce conditioned pain modulation (CPM) that activates a descending endogenous analgesic mechanism. The treatment is self-administered and controlled by a smartphone application.
Sponsors
Theranica
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Participants aged 18-75 years old. 2. Participants meeting the ICHD-3 diagnostic criteria for chronic migraine 3. Participants have personal access to a smartphone 4. Participants must be able and willing to comply with the protocol 5. Participants must be able and willing to provide written informed consent
Exclusion criteria
1. Participants with an implanted electrical and/or neurostimulator device (e.g. cardiac pacemaker, cochlear implant). 2. Participants with congestive heart failure (CHF), severe cardiac or cerebrovascular disease. 3. Participants with uncontrolled epilepsy. 4. Lack of efficacy, after an adequate therapeutic trial, of at least two migraine specific acute medications 5. Change in migraine preventive medications (type or dose) in the last two months prior to recruitment and/or during the study 6. Pregnant, trying to get pregnant or breastfeeding female participants 7. Subjects participating in any other interventional clinical study. 8. Participants without basic cognitive and motor skills needed to operate a smartphone 9. Participants with other significant pain, medical or psychological problems that in the opinion of the investigator may confound the study assessments 10. Participants who have previous experience with the device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Reduction of Migraine Headache at 2 Hours Post Treatment | 2 hours post-treatment | The proportion of participants reporting pain relief at 2 hours post-treatment without the use of rescue medication following the test treatment . Pain relief is defined as an improvement from severe or moderate pain to mild or no pain, or from mild pain to no pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Disappearance of Phonophobia at 2 Hours Post-treatment | 2 hours post treatment | The proportion of participants reporting disappearance phonophobia at 2 hours post-treatment without rescue medications following the test treatment. |
| Proportion of Participants With Pain Disappearance at 2 Hours Post Treatment | 2 hours post treatment | The proportion of participants reporting freedom from migraine pain at 2 hours post-treatment without medications following the test treatment. Pain freedom is defined as an improvement from severe or moderate or mild pain to no pain |
| Proportion of Participants With Disappearance of Nausea and/or Vomiting at 2 Hours Post-treatment | 2 hours post treatment | The proportion of participants reporting disappearance of nausea and/or vomiting at 2 hours post-treatment without rescue medications following the test treatment. |
| Proportion of Participants With Disappearance of Photophobia at 2 Hours Post-treatment | 2 hours post treatment | The proportion of participants reporting disappearance of photophobia at 2 hours post-treatment without rescue medications following the test treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Within-patient Consistency - Percentage of Participants With Reduction in Headache Pain in at Least 50% of Their Treatments | 4 weeks | Proportions of participants achieving pain relief at 2 hours in at least 50% of all their treatments (excluding the training treatment) |
| Within-patient Consistency - Percentage of Participants Free of Headache Pain in at Least 50% of Their Treatments | 4 weeks | Proportion of participants achieving pain free at 2 hours in at least 50% of all their treatments (excluding the training treatment) |
| Proportion of Participants With Improve Functional Disability at 2 Hours Post-treatment | 2 hours post treatment | The proportion of participants achieving improvement of at least one grade in functional disability in the test treatment at 2 hours post-treatment with no use of rescue medication. the scale used was: (0) No limitation, (1) Some limitation, (2) Moderate limitation and (3) Severe limitation. |
| Proportion of Participants With Improve Functional Disability at 24 Hours Post-treatment | 24 hours post treatment | The proportion of participants achieving improvement of at least one grade in functional disability in the test treatment at 24 hours post-treatment with no use of rescue medication. the scale used was: (0) No limitation, (1) Some limitation, (2) Moderate limitation and (3) Severe limitation. |
Countries
Israel, United States
Participant flow
Recruitment details
This study was conducted from September 18, 2019 to February 18, 2020. . Study sites were Nuvance health (Poughkeepsie, NY) and Meir Medical center (Kefar Sava, Israel). 42 patients were enrolled and received a device. Two participants withdrew from the study. All participants completed at least one treatment (the training treatment) and 38 participants completed the test treatment, forming the final analysis set.
Participants by arm
| Arm | Count |
|---|---|
| Nerivio Device Treatment participant will receive the Nerivio device for treating their migraine attacks. Treatment will be perform as soon as the participant feel that the migraine attack started
Nerivio: The device delivers transcutaneous electrical stimulation to the upper arm to induce conditioned pain modulation (CPM) that activates a descending endogenous analgesic mechanism. The treatment is self-administered and controlled by a smartphone application. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Performed only 1 treatment | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Nerivio Device Treatment |
|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 14.8 |
| Average number of headache days per month | 21.5 Days per month STANDARD_DEVIATION 6.3 |
| Average number of migraine headache das per month | 18.3 Days per month STANDARD_DEVIATION 6.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 42 Participants |
| Region of Enrollment Israel | 12 participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 7 Participants |
| Use of preventive medication | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 42 |
| other Total, other adverse events | 1 / 42 |
| serious Total, serious adverse events | 0 / 42 |
Outcome results
Primary
Proportion of Participants With Reduction of Migraine Headache at 2 Hours Post Treatment
The proportion of participants reporting pain relief at 2 hours post-treatment without the use of rescue medication following the test treatment . Pain relief is defined as an improvement from severe or moderate pain to mild or no pain, or from mild pain to no pain.
Time frame: 2 hours post-treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nerivio Device Treatment | Proportion of Participants With Reduction of Migraine Headache at 2 Hours Post Treatment | 19 Participants |
Secondary
Proportion of Participants With Disappearance of Nausea and/or Vomiting at 2 Hours Post-treatment
The proportion of participants reporting disappearance of nausea and/or vomiting at 2 hours post-treatment without rescue medications following the test treatment.
Time frame: 2 hours post treatment
Population: only 17 participants reported nausea and/or vomiting at T=0 hours of the Test treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nerivio Device Treatment | Proportion of Participants With Disappearance of Nausea and/or Vomiting at 2 Hours Post-treatment | 10 Participants |
Secondary
Proportion of Participants With Disappearance of Phonophobia at 2 Hours Post-treatment
The proportion of participants reporting disappearance phonophobia at 2 hours post-treatment without rescue medications following the test treatment.
Time frame: 2 hours post treatment
Population: only 16 participants reported phonophobia at T=0 hours of the Test treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nerivio Device Treatment | Proportion of Participants With Disappearance of Phonophobia at 2 Hours Post-treatment | 8 Participants |
Secondary
Proportion of Participants With Disappearance of Photophobia at 2 Hours Post-treatment
The proportion of participants reporting disappearance of photophobia at 2 hours post-treatment without rescue medications following the test treatment.
Time frame: 2 hours post treatment
Population: only 24 participants reported photophobia at T=0 hours of the Test treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nerivio Device Treatment | Proportion of Participants With Disappearance of Photophobia at 2 Hours Post-treatment | 9 Participants |
Secondary
Proportion of Participants With Pain Disappearance at 2 Hours Post Treatment
The proportion of participants reporting freedom from migraine pain at 2 hours post-treatment without medications following the test treatment. Pain freedom is defined as an improvement from severe or moderate or mild pain to no pain
Time frame: 2 hours post treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nerivio Device Treatment | Proportion of Participants With Pain Disappearance at 2 Hours Post Treatment | 10 Participants |
Other Pre-specified
Proportion of Participants With Improve Functional Disability at 24 Hours Post-treatment
The proportion of participants achieving improvement of at least one grade in functional disability in the test treatment at 24 hours post-treatment with no use of rescue medication. the scale used was: (0) No limitation, (1) Some limitation, (2) Moderate limitation and (3) Severe limitation.
Time frame: 24 hours post treatment
Population: Only 19 participants reported their function disability level at T=0 hours and T=24 hours for their test treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nerivio Device Treatment | Proportion of Participants With Improve Functional Disability at 24 Hours Post-treatment | 15 Participants |
Other Pre-specified
Proportion of Participants With Improve Functional Disability at 2 Hours Post-treatment
The proportion of participants achieving improvement of at least one grade in functional disability in the test treatment at 2 hours post-treatment with no use of rescue medication. the scale used was: (0) No limitation, (1) Some limitation, (2) Moderate limitation and (3) Severe limitation.
Time frame: 2 hours post treatment
Population: Only 30 participants reported their function disability level at T=0 hours and T=2 hours for their test treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nerivio Device Treatment | Proportion of Participants With Improve Functional Disability at 2 Hours Post-treatment | 14 Participants |
Other Pre-specified
Within-patient Consistency - Percentage of Participants Free of Headache Pain in at Least 50% of Their Treatments
Proportion of participants achieving pain free at 2 hours in at least 50% of all their treatments (excluding the training treatment)
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nerivio Device Treatment | Within-patient Consistency - Percentage of Participants Free of Headache Pain in at Least 50% of Their Treatments | 10 Participants |
Other Pre-specified
Within-patient Consistency - Percentage of Participants With Reduction in Headache Pain in at Least 50% of Their Treatments
Proportions of participants achieving pain relief at 2 hours in at least 50% of all their treatments (excluding the training treatment)
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nerivio Device Treatment | Within-patient Consistency - Percentage of Participants With Reduction in Headache Pain in at Least 50% of Their Treatments | 27 Participants |