Efficacy and Safety of Nerivio™ for Acute Treatment of Migraine in People With Chronic Migraine

• Sponsor: Theranica (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04161807
• Collaborator: (none)
• Enrollment: 42
• Locations: 2
• Arm: 1
• Actual Duration (Months): 5
• Patients Per Site: 21
• Patients Per Site Per Month: 4.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Migraine	Device: Nerivio	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Nerivio™, a Remote Electrical Neuromodulation Device, for Acute Treatment of Migraine in People With Chronic Migraine: an Open Label, Single Arm, Multicenter Study
• Actual Study Start Date: Sep 18, 2019
• Actual Primary Completion Date: Feb 18, 2020
• Actual Study Completion Date: Feb 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Device: 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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.

3. 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.

4. 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.

Other Outcome Measures

1. 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)

2. 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)

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Health Quest Medical Practice, PC	Lagrangeville	New York	United States	12540
2	Meir Medical Center	Kfar Saba		Israel	4428164

Sponsors and Collaborators

• Theranica

Investigators

• Principal Investigator: Paul Wright, Nuvance Health

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 16, 2019
• Informed Consent Form - Jul 18, 2019

More Information

Publications

None provided.

• Responsible Party: Theranica
• ClinicalTrials.gov Identifier: NCT04161807
• Other Study ID Numbers: TCH005
• First Posted: Nov 13, 2019
• Last Update Posted: Feb 16, 2021
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Migraine Disorders

Study Results

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.

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Period Title: Overall Study
STARTED	42
COMPLETED	38
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Overall Participants	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.1 (14.8)
Sex: Female, Male (Count of Participants)
Female	35 83.3%
Male	7 16.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	42 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	30 71.4%
Israel	12 28.6%
Average number of headache days per month (Days per month) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days per month]	21.5 (6.3)
Average number of migraine headache das per month (Days per month) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days per month]	18.3 (6.6)
Use of preventive medication (Count of Participants)
Count of Participants [Participants]	27 64.3%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Reduction of Migraine Headache at 2 Hours Post Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Measure Participants	38
Count of Participants [Participants]	19 45.2%

2. Secondary Outcome

Title	Proportion of Participants With Pain Disappearance at 2 Hours Post Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Measure Participants	38
Count of Participants [Participants]	10 23.8%

3. Secondary Outcome

Title	Proportion of Participants With Disappearance of Nausea and/or Vomiting at 2 Hours Post-treatment
Description	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

Outcome Measure Data

Analysis Population Description

only 17 participants reported nausea and/or vomiting at T=0 hours of the Test treatment

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Measure Participants	17
Count of Participants [Participants]	10 23.8%

4. Secondary Outcome

Title	Proportion of Participants With Disappearance of Photophobia at 2 Hours Post-treatment
Description	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

Outcome Measure Data

Analysis Population Description

only 24 participants reported photophobia at T=0 hours of the Test treatment

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Measure Participants	24
Count of Participants [Participants]	9 21.4%

5. Secondary Outcome

Title	Proportion of Participants With Disappearance of Phonophobia at 2 Hours Post-treatment
Description	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

Outcome Measure Data

Analysis Population Description

only 16 participants reported phonophobia at T=0 hours of the Test treatment

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Measure Participants	16
Count of Participants [Participants]	8 19%

6. Other Pre-specified Outcome

Title	Within-patient Consistency - Percentage of Participants With Reduction in Headache Pain in at Least 50% of Their Treatments
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Measure Participants	38
Count of Participants [Participants]	27 64.3%

7. Other Pre-specified Outcome

Title	Within-patient Consistency - Percentage of Participants Free of Headache Pain in at Least 50% of Their Treatments
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Measure Participants	38
Count of Participants [Participants]	10 23.8%

8. Other Pre-specified Outcome

Title	Proportion of Participants With Improve Functional Disability at 2 Hours Post-treatment
Description	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

Outcome Measure Data

Analysis Population Description

Only 30 participants reported their function disability level at T=0 hours and T=2 hours for their test treatment

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Measure Participants	30
Count of Participants [Participants]	14 33.3%

9. Other Pre-specified Outcome

Title	Proportion of Participants With Improve Functional Disability at 24 Hours Post-treatment
Description	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

Outcome Measure Data

Analysis Population Description

Only 19 participants reported their function disability level at T=0 hours and T=24 hours for their test treatment

Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
Measure Participants	19
Count of Participants [Participants]	15 35.7%

Adverse Events

Time Frame	Up to 4 weeks
Adverse Event Reporting Description	The Nerivio device is a neurostimulator and it is externally applied over the body.The Nerivio is accepted as a non-significant risk (NSR) device. In addition, as theexclusion criteria for the study leave out participant with electrical implant,congenital heart failure or epilepsy, the number of high risk participants is zero.
Arm/Group Title	Nerivio Device Treatment
Arm/Group Description	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.
All Cause Mortality
	Nerivio Device Treatment
	Affected / at Risk (%)	# Events
Total	0/42 (0%)
Serious Adverse Events
	Nerivio Device Treatment
	Affected / at Risk (%)	# Events
Total	0/42 (0%)
Other (Not Including Serious) Adverse Events
	Nerivio Device Treatment
	Affected / at Risk (%)	# Events
Total	1/42 (2.4%)
Skin and subcutaneous tissue disorders
Tingling	1/42 (2.4%)	1

Limitations/Caveats

No limitations or caveats were reported

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.