Clinical trial NCT04828707: Assessment of Safety and Efficacy of Nerivio for the Migraine Prevention
Official title: A Prospective, Randomized, Double-blind, Sham-controlled Multi-center Clinical Study Assessing the Safety and Efficacy of Nerivio for the Preventive Treatment of Migraine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Migraine
Lead sponsor: Theranica
Sponsor class: INDUSTRY
First posted: 2021-04-02
Enrollment: 335
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, sham-controlled
Primary purpose: PREVENTION

Brief summary: Migraine is a common neurologic with attacks of headache and associated symptoms such as nausea, vomiting, phono and photophobia. Migraine can lead to substantial functional impairment. This study intends to demonstrate the safety and efficacy of the Nerivio for migraine prevention.

The study is a prospective, randomized, double-blind, sham-controlled, multicenter study, conducted in three phases.

The study will consist of a screening/enrollment visit, followed by a 4-week (28 days) baseline phase, an 8-week double-blind preventive treatment phase, and a 4-week open-label phase.

Patients will complete an electronic diary throughout the study; this includes a daily evening report (completed regardless of whether the patient had a headache) and treatment feedback during the follow-up pre-emptive phase.

The primary endpoint is the mean change in the average of migraine headache days per month comparing the 4-week baseline phase (weeks 1 through 4) with the last 28 days of the treatment phase (weeks 9 through 12).

Detailed description: Nerivio is a neuromodulation device approved for the acute treatment of migraine with or without aura in patients 12 years of age or older. The device utilizes electro stimulation to achieve conditioned pain modulation (CPM). CPM stimulate endogenous analgesic mechanism. Treatments are self-administered by the user at the onset of a migraine attack. this study intends to demonstrate the safety and efficacy of the Nwrivio for migraine prevention.

The study is a prospective, randomized, double-blind, sham-controlled, multicenter trial, conducted in three phases. The ratio between treatment and control groups will be 1:1, stratified by center and patient type (chronic/non-chronic). The study will consist of a screening/enrollment visit, followed by a 4-week (28 days) baseline phase. Eligible participants will enter an 8-week double-blind preventive treatment phase. Following the preventive treatment phase, patients will be offered to participate in a 4-week open-label pre-emptive treatment phase or continue their prevention treatment with an active device, according to their eligibility.

Patients will complete an electronic diary throughout the study; this includes a daily evening report (completed regardless of whether the patient had a headache) and treatment feedback during the follow up pre-emptive phase

Phase I - Baseline - 4 weeks (weeks 1 through 4):

Eligible participants will install the Nerivio app on their smartphones and will be instructed to record daily their migraine/headaches symptoms and medication use on the Nerivio app.

Transition to the treatment phase: Participants who meet the following criteria in the baseline phase will be eligible to continue to the treatment phase:

* Complete the diary in at least 22 out of the 28 days during the baseline phase (80%)
* Have between 6 to 24 headache days during the 28-day baseline period
* At least 4 of their headache days during the baseline phase fulfill the International Classification of Headache Disorders 3rd edition (ICHD-3) criteria for migraine (migraine without aura \[code 1.1; C and D\] or with aura \[code 1.2; B and C\], or probable migraine, or headaches requiring the use of migraine-specific medications including triptans, gepants or ergot derivatives).

Phase II - treatment phase (prevention) - 8 weeks (weeks 5 through 12):

Participants who meet the baseline phase requirements will be randomized in a 1:1 ratio to active and sham groups. Participants will be instructed to complete a daily diary (in the Nerivio app) about their headaches, associated symptoms, and medication use. They will also be instructed to conduct a 45-minute treatment with Nerivio every other day.

Transition to the follow-up phase (open label):

At the end of the treatment phase, participants from both arms (active and sham) may continue to a follow-up phase in which they will receive an active device that can be used during this phase. The data of all participants will be used for safety analyses.

The data of participants from the baseline and treatment phases will be used to assess their eligibility to participate in the pre-emptive follow-up phase. Participants eligible for the follow-up phase meet the following conditions:

* Between 6-16 headache days during the baseline phase.
* Participants experience prodrome symptoms within 24 hours prior to the onset of their migraine headache in at least half of their migraine attacks during the baseline phase.
* Participants completed the daily questionnaires in at least 70% of the days during the treatment phase.
* Treated every other day in at least 24 and less than 33 days during the 56 days of the treatment phase.

All adverse events will be reported.

Phase III - Follow-up phase (open label) - 4 weeks (weeks 13 through 16):

All participants will receive an active Nerivio device to use during the follow-up phase. Participants who do not meet the above requirements will be able to enter into the safety follow-up and continue to use Nerivio every other day for the preventive treatment of migraine. They will be instructed to compete a daily diary as was done in the treatment phase.

Participants who meet the above requirements will enter the pre-emptive follow-up phase and be instructed to conduct a 45-minute device treatment within 60 minutes of prodrome symptom onset. Participants will be instructed to complete questionnaires regarding their headache, prodrome symptoms, and medication use at baseline (start of treatment), 2 hours post-treatment, and 24 hours post-treatment. In addition, participants will be instructed to continue to report the daily diary, as performed in the other phases of the study.

All adverse events will be reported.

Eligibility criteria: Inclusion Criteria:

1. Age 18-75 years old.
2. Must have at least a 6-month history of headaches that meet the ICHD-3 diagnostic criteria for migraine with or without aura, either chronic (at least 15 days of Headache Days(HD)/ month with migraine days (migraine with or without aura) at least 8 days/ month for \> 3 months) or non-chronic migraine.
3. History of 6 to 24 headache days per 28-day period for each of the 3 months preceding study enrolment (based on participant report).
4. Subject on prophylactic migraine treatment are permitted to remain on 1 medication with possible migraine-prophylactic effects if the dose has been stable for at least 2 months prior to the screening visit, and the dose is not expected to change during the course of the study.
5. Have personal access to a smartphone (24/7).
6. Must be able and willing to comply with the protocol.
7. Must be able and willing to provide informed consent..

Exclusion Criteria:

1. An active implanted electrical and/or neurostimulator device (e.g. cardiac pacemaker, cochlear implant).
2. Uncontrolled epilepsy.
3. History of use of opioids or barbiturates on more than 4 days a month in the last 6 months.
4. Current participation in any other interventional clinical study
5. Subject without basic cognitive and motor skills required for operating a smartphone.
6. Pregnant or breastfeeding.
7. Other significant pain, medical or psychological problems that in the opinion of the investigator may confound the study assessments.
8. Prior experience with the Nerivio device.

Primary outcomes:
measure: Reduction in Migraine Days
timeFrame: 3 months
measure: Rate of Adverse Events (Safety and Tolerability)
timeFrame: 3 months
Secondary outcomes:
measure: Reduction in Moderate/Severe Headache Days
timeFrame: 3 months
measure: Reduction Headache Days
timeFrame: 3 months
measure: Reduction of 50% in Headache Days
timeFrame: 3 months
measure: Increase in Headache Impact Test-6 (HIT-6) Score at the End of the Last 28 Days (4 Weeks) of the Treatment Phase (Weeks 9 Through 12) Compare to the HIT-6 Score at the End of the 4-week Baseline Phase (Weeks 1 Through 4)
timeFrame: 3 months
measure: Reduction in Migraine-Specific Quality-of-Life (MSQ) Questionnaire Score at the End of the Last 28 Days (4 Weeks) of the Treatment Phase (Weeks 9 Through 12) Compare to the MSQ Score at the End of the 4-week Baseline Phase (Weeks 1 Through 4)
timeFrame: 3 months
Other outcomes:
measure: Reduction in Migraine Medication Intake
timeFrame: 3 months
measure: Percentage of Freedom From Headache Post 2 Hours Following Prodrome Treatment
timeFrame: 2 hours post treatment at follow up phase
measure: Percentage of Freedom From Headache Post 24 Hours Following Prodrome Treatment
timeFrame: 24 hours post treatment at follow up phase
measure: Percentage of Reduction of Headache Post 24 Hours From Prodrome Treatment
timeFrame: 24 hours post treatment at follow up phase
measure: Feasibility of Migraine Prediction Algorithm
timeFrame: 3 months
measure: Health Economic Analysis
timeFrame: 12 weeks
Locations:
city: Phoenix
country: United States
facility: Evolve Clinical Research
state: Arizona
city: Carlsbad
country: United States
facility: The Neurology Center of Southern California
state: California
city: Newport Beach
country: United States
facility: Newport Beach Clinical Research Associates
state: California
city: Hartford
country: United States
facility: Hartford Headache Center
state: Connecticut
city: Boynton Beach
country: United States
facility: RecioMed Clinical Research
state: Florida
city: Cutler Bay
country: United States
facility: Beautiful Minds Clinical Research Center
state: Florida
city: Chicago
country: United States
facility: Chicago Headache Center and Research Institute
state: Illinois
city: Evansville
country: United States
facility: Deaconess Clinic
state: Indiana
city: Paducah
country: United States
facility: Four Rivers Clinical Research
state: Kentucky
city: Ridgeland
country: United States
facility: Headache Neurology Research Institute
state: Mississippi
city: Saint Peters
country: United States
facility: StudyMetrix Research
state: Missouri
city: Springfield
country: United States
facility: ClinVest Research
state: Missouri
city: Toms River
country: United States
facility: Ocean medical research
state: New Jersey
city: Amherst
country: United States
facility: DENT Neurosciences Research Center
state: New York
city: Columbia
country: United States
facility: Prevention & Strengthening Solutions, Inc.
state: South Carolina
city: Morgantown
country: United States
facility: West Virginia University Medicine
state: West Virginia
Study officials:
affiliation: Stanford Health Care
name: Robert Cowan, MD
role: STUDY_CHAIR
References: