Safety and Efficacy of Nerivio™ for the Acute Treatment of Migraine in Adolescents

• ClinicalTrials.gov Identifier: NCT04089761
• Recruitment Status: Terminated
• First Posted: September 13, 2019
• Results First Posted: February 25, 2021
• Last Update Posted: February 25, 2021
• Sponsor: Theranica
• Information provided by (Responsible Party): Theranica

Study Description

Brief Summary:

Nerivio™ is an FDA-authorized remote electrical neuromodulation (REN) device for the acute treatment of migraine with or without aura in patients 18 years old or above who do not have 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.

This is a prospective, single arm, open label, multicenter trial of the safety and efficacy of Nerivio™ for the acute treatment of migraine in adolescents

The study will be conducted in three phases:

Phase I - Run-in:

Phase II - Treatment phase:

Phase III (optional) - Free-use

Condition or disease	Intervention/treatment	Phase
Acute Migraine	Device: Nerivio	Not Applicable

Detailed Description:

This open label study includes 3 phases and up to 4 visits. All visits will be conducted in the presence of a parent/guardian.

First visit - enrollment: The first visit will include screening, enrollment and training on the application in diary mode. The screening process will include an eligibility assessment and a urine pregnancy test. Following successful screening, enrollment interview and signing an informed consent by the parent/guardian and an informed assent by the participant. The participants will be trained to use the electronic diary application, installed on their own smartphones. The site personnel will be required to document the training session in the CRF. During this visit, participants will complete baseline questionnaires that included information on the frequency and severity of their migraine attacks, typical associated symptoms, use of preventive and acute treatments, and the effect that their migraine attacks have on their daily routine and quality of life.

Phase 1 - run-in phase: After the enrollment visit, participants will undergo a 4-week migraine diary phase aimed to collect baseline migraine characteristics and further assess eligibility. Participants will be asked to report in the application each migraine attack. These reports will be transferred by the application to the electronic data collection (EDC) system, where they will be collected and registered. Participants who did not have at least 3 migraine attacks will be excluded from the study. Eligibility will also be determined based on the compliance of participants to report the attacks within one hour from attack onset and report the pain level at 2 hours post-treatment in at least 66.7% of the reported attacks.

Second visit - Device training visit: Eligible participants who meet the run-in requirements will receive the Nerivio™ device. The device will be registered and connected by Bluetooth to their smartphone. During this visit, participants and their parent/guardian will be trained to use the device, including finding the optimal individual stimulation intensity level (perceptible but not painful). The site will also carefully review with the patient and parent/caregiver how to identify a qualifying migraine attack (see below) and provide detailed instructions on study procedures.

The individual intensity level identified during this visit will be recorded, and the participants will be asked to treat their migraine headaches with the device using the identified intensity. If the research staff recognizes that the participant cannot tolerate the feeling of the electrical stimulation, the participant may be withdrawn from the study.

Phase 2 -Treatment phase: Participants will be instructed to use the device for the treatment of 4 qualifying migraine attacks (see below) as soon as possible and always within 60 minutes of onset during a period of up to 8 weeks. Participants will be instructed to use the device with the intensity level identified during the device training visit (with a range of ±5 units) 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. The participants will use the app to record pain intensity levels (none, mild, moderate, or severe) at baseline, 2- and 24-hours post-treatment, and to record the presence/absence of associated migraine symptoms (nausea, photophobia, phonophobia) at baseline and 2 hours post-treatment. To assess functional disability, participants will also record at baseline, 2- and 24-hours post-treatment their response to the following question in their diary: "How do you rate your ability to do school-work or perform your usual activities?" using a 4-point scale ('as usual', 'some ability', 'a little ability', 'no ability at all'). 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.

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. Attacks 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").

Third visit - Termination of the treatment phase and free-use phase initiation: Following the 8-week period of the treatment phase, participants will return to the clinic to return the device and fill questionnaires assessing satisfaction and user experience. All participants who complete the treatment phase will be offered to participate in an additional 8-week phase in which the device can be incorporate into usual care.

Phase 3 - Free-use phase: Participants will continue in an 8-week phase in which they will be able to use the device according to their preferences for the treatment of their migraine attacks.

Fourth (final) visit - End of study: Participants will return to the clinic following the end of the 8-week free-use phase, at which time they will return the device.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: single arm, open-label, multicenter study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single Arm, Open Label, Multicenter Study of the Safety and Efficacy of Nerivio™ for the Acute Treatment of Migraine in Adolescents
• Actual Study Start Date: October 1, 2019
• Actual Primary Completion Date: May 10, 2020
• Actual Study Completion Date: May 24, 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: Active Device; Treatment of acute migraine with an active form of Nerivio device

Device: Nerivio; Nerivio™ is an FDA-authorized remote electrical neuromodulation (REN) device for the acute treatment of migraine with or without aura in patients 18 years old or above who do not have 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 treatment is self-administered and controlled by a smartphone application.

Outcome Measures

Primary Outcome Measures :

1. Safety of Nerivio Device [ Time Frame: 12 weeks ]
   Number of Participants with Device-Related Adverse Events

Secondary Outcome Measures :

1. Pain Relief at 2 Hours Post Treatment [ Time Frame: 2 hours post treatment ]
   The percentage of subjects reporting, for the test treatment, pain relief at 2 hours post-treatment without the use of rescue medication. Pain relief is defined as an improvement from severe or moderate pain to mild or no pain, or from mild pain to no pain. Pain level was reported using a 4-point Likert scale (0 -No pain, 1 - Mild pain, 2 - Moderate pain, 3- Severe pain)
2. Pain-free at 2 Hours Post Treatment [ Time Frame: 2 hours post treatment ]
   The percentage of subjects reporting, for the test treatment, no pain at 2 hours post-treatment without the use of rescue medication. Pain-free is defined as improvement from mild, moderate, or severe pain to no pain. Pain level was reported using a 4-point Likert scale (0 - No pain, 1 - Mild pain, 2 - Moderate pain, 3- Severe pain)
3. Disappearance of Nausea at 2 Hours Post-treatment [ Time Frame: 2 hours post treatment ]
   The percentage of subjects presented nausea at the baseline (T=0 hours) and reported disappearance of nausea at 2 hours post-treatment of the test treatment
4. Disappearance of Photophobia at 2 Hours Post Treatment [ Time Frame: 2 hors post treatment ]
   The percentage of subjects presented photophobia at baseline (T=0 hours) and reported disappearance of photophobia at 2 hours post-treatment of the test treatment
5. Disappearance of Phonophobia at 2 Hours Post Treatment [ Time Frame: 2 hours post treatment ]
   The percentage of subjects presented phonophobia at baseline (T=0 hours) and reported disappearance of phonophobia at 2 hours post-treatment of the test treatment

Other Outcome Measures:

1. Sustained Pain Relief at 24 Hours Post Treatment [ Time Frame: 24 hours post treatment ]
   The percentage of subjects achieving, for the test treatment, pain relief at 2 hours post-treatment without the use of rescue medication and no relapse of headache pain within 24 hours
2. Sustained Pain Free at 24 Hours Post Treatment [ Time Frame: 24 hours post treatment ]
   The percentage of subjects achieving, for the test treatment, freedom from pain at 2 hours post-treatment without the use of rescue medication and no relapse of headache pain within 24 hours
3. Functional Disability at 2 Hours Post Treatment [ Time Frame: 2 hours post treatment ]
   The percentage of subjects 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
4. Functional Disability at 24 Hours Post Treatment [ Time Frame: 24 hours post treatment ]
   The percentage of subjects 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

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Participants age 12-17 years old at the time of informed consent, inclusive. 2. Participants have at least a 6-month history of headaches that meet the ICHD-3 diagnostic criteria for migraine with or without aura 3. History of at least 3 migraine attacks per month for each of the 2 months preceding study enrolment 4. Typical headache duration of at least 3 hours (when untreated or unsuccessfully treatment) 5. Stable migraine preventive medications during the 2 months prior to enrollment (no change in usage or dosage).

6. Participants have personal access to a smartphone (24/7) 7. Participants must be able and willing to comply with the protocol 8. Parents/Guardians must be able and willing to provide written informed consent 9. Participants must be able and willing to provide informed assent

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 epilepsy.
4. Medical use of cannabis or recreational use one month prior to enrollment.
5. Participants who have undergone nerve block (occipital or other) in the head or neck within the last 2 weeks
6. Treatment with onabotulinum toxin A (Botox) to the head and/or neck for 3 months before enrollment and/or during the study
7. Any history of anti-CGRP antibody treatment
8. Current participation in any other clinical study that includes treatment
9. Participants without basic cognitive and motor skills required for operating a smartphone.
10. Pregnant or breastfeeding females
11. Pure menstrual migraine
12. Participants who received parenteral treatments for migraine within the previous 2 weeks.
13. Participants with other significant pain, medical or psychological problems that in the opinion of the investigator may confound the study assessments
14. Participants who have previous experience with the device
15. Participants with arm circumference below 7.9 inches (20 cm)

Contacts and Locations

Locations

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

United States, Florida

Clinical Trials Solutions

Hialeah, Florida, United States, 33012

Nicklaus children hospital

Miami, Florida, United States, 33155

United States, Georgia

PANDA neurology

Atlanta, Georgia, United States, 30328

United States, Louisiana

Children Hospital New Orleans

New Orleans, Louisiana, United States, 70118

United States, Missouri

Children Mercy Kansas City

Kansas City, Missouri, United States, 64108

United States, New York

DENT neurology clinic

Amherst, New York, United States, 14226980

NYU Langone-Health

New York, New York, United States, 10017

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, United States, 19178

United States, Texas

Mercury Clinical Research

Houston, Texas, United States, 77036

Texas Children's Hospital, Baylor College of Medicine

Houston, Texas, United States, 77094

Sponsors and Collaborators

Theranica

Investigators

• Principal Investigator: Andrew Hershey, MD; Director, Headache Center Cincinnati Children's Hospital Medical Center

  Study Documents (Full-Text)

Documents provided by Theranica:

Study Protocol and Statistical Analysis Plan  [PDF] July 1, 2019

Informed Consent Form  [PDF] July 1, 2019

More Information

• Responsible Party: Theranica
• ClinicalTrials.gov Identifier: NCT04089761
• Other Study ID Numbers: TCH004
• First Posted: September 13, 2019
• Results First Posted: February 25, 2021
• Last Update Posted: February 25, 2021
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• 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

Keywords provided by Theranica:

Migraine treatment, Adolescence

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases