Clinical trial NCT04089761: Safety and Efficacy of Nerivio™ for the Acute Treatment of Migraine in Adolescents
Official title: A Single Arm, Open Label, Multicenter Study of the Safety and Efficacy of Nerivio™ for the Acute Treatment of Migraine in Adolescents
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Migraine
Keywords: Migraine treatment, Adolescence
Lead sponsor: Theranica
Sponsor class: INDUSTRY
First posted: 2019-09-13
Enrollment: 60
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: single arm, open-label, multicenter study
Primary purpose: TREATMENT

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

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.

Eligibility 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)

Primary outcomes:
measure: Safety of Nerivio Device
timeFrame: 12 weeks
Secondary outcomes:
measure: Pain Relief at 2 Hours Post Treatment
timeFrame: 2 hours post treatment
measure: Pain-free at 2 Hours Post Treatment
timeFrame: 2 hours post treatment
measure: Disappearance of Nausea at 2 Hours Post-treatment
timeFrame: 2 hours post treatment
measure: Disappearance of Photophobia at 2 Hours Post Treatment
timeFrame: 2 hors post treatment
measure: Disappearance of Phonophobia at 2 Hours Post Treatment
timeFrame: 2 hours post treatment
Other outcomes:
measure: Sustained Pain Relief at 24 Hours Post Treatment
timeFrame: 24 hours post treatment
measure: Sustained Pain Free at 24 Hours Post Treatment
timeFrame: 24 hours post treatment
measure: Functional Disability at 2 Hours Post Treatment
timeFrame: 2 hours post treatment
measure: Functional Disability at 24 Hours Post Treatment
timeFrame: 24 hours post treatment
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hialeah
country: United States
facility: Clinical Trials Solutions
state: Florida
city: Miami
country: United States
facility: Nicklaus children hospital
state: Florida
city: Atlanta
country: United States
facility: PANDA neurology
state: Georgia
city: New Orleans
country: United States
facility: Children Hospital New Orleans
state: Louisiana
city: Kansas City
country: United States
facility: Children Mercy Kansas City
state: Missouri
city: Amherst
country: United States
facility: DENT neurology clinic
state: New York
city: New York
country: United States
facility: NYU Langone-Health
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (CHOP)
state: Pennsylvania
city: Houston
country: United States
facility: Mercury Clinical Research
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital, Baylor College of Medicine
state: Texas
Study officials:
affiliation: Director, Headache Center Cincinnati Children's Hospital Medical Center
name: Andrew Hershey, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hershey AD, Irwin S, Rabany L, Gruper Y, Ironi A, Harris D, Sharon R, McVige J. Comparison of Remote Electrical Neuromodulation and Standard-Care Medications for Acute Treatment of Migraine in Adolescents: A Post Hoc Analysis. Pain Med. 2022 Apr 8;23(4):815-820. doi: 10.1093/pm/pnab197.