The RIME Study - Combined Occipital and Supraorbital Transcutaneous Nerve Stimulation for Treatment of Migraine

• ClinicalTrials.gov Identifier: NCT03631550
• Recruitment Status: Completed
• First Posted: August 15, 2018
• Results First Posted: July 12, 2022
• Last Update Posted: September 22, 2022
• Sponsor: Neurolief Ltd.
• Information provided by (Responsible Party): Neurolief Ltd.

Study Description

Brief Summary:

this study will evaluate the clinical performance and safety of a self administered abortive treatment for migraine headache using combined occipital and supraorbital transcutaneous nerve stimulator (Neurolief device, Relivion®)

Condition or disease	Intervention/treatment	Phase
Acute Migraine	Device: Relivion active; Device: Relivion Sham	Not Applicable

Detailed Description:

The Relivion® is a non-invasive transcutaneous neuro-stimulator is indicated for the acute treatment of migraine with or without aura in subjects 18 years of age or older. The Relivion® is intended to be a prescription device, self-used at home.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 187 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The RIME Study - Combined Occipital and Supraorbital Transcutaneous Nerve Stimulation for Treatment of Migraine
• Actual Study Start Date: November 29, 2018
• Actual Primary Completion Date: August 4, 2020
• Actual Study Completion Date: August 4, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Active; Relivion Active device	Device: Relivion active; 1 hour self-administered occipital and supraorbital transcutaneous nerve stimulation
Sham Comparator: Sham; Relivion Sham device	Device: Relivion Sham; 1 hour self-administered Sham occipital and supraorbital transcutaneous nerve stimulation

Outcome Measures

Primary Outcome Measures :

1. Proportion of Subjects Reporting Reduction of Migraine Headache Pain at 2 Hours From Treatment Initiation [ Time Frame: 2 hours from treatment initiation ]
   the number and percent of subjects reporting reduction of migraine headache pain 2 hours post treatment initiation from severe or moderate to mild or no pain, or from mild to no pain, in their first eligible treated migraine attack (if rescue therapy was not used)

Secondary Outcome Measures :

1. Proportion of Subjects Reporting Improvement in Their Most Bothersome Symptom (MBS) Other Than a Headache, 2 Hours Post-treatment Initiation [ Time Frame: 2 hours from treatment initiation ]
   The number and percentage of subjects reporting improvement in their Most Bothersome Symptom (MBS) other than a headache, 2 hours post-treatment initiation (if rescue therapy was not used), in their first eligible treated migraine attack. MBS may be nausea, photophobia, phonophobia
2. Proportion of Subjects Reporting Reduction of Migraine Headache Pain 1-hour Post Treatment Initiation [ Time Frame: 1 hour from treatment initiation ]
   The number and percentage of subjects reporting reduction of migraine headache pain 1-hour post treatment initiation (if rescue therapy was not used), from severe or moderate to mild or no pain, or from mild to no pain, in their first eligible treated migraine attack
3. Proportion of Subjects Who Are Pain Free at 2 Hours Post Treatment Initiation [ Time Frame: 2 hours from treatment initiation ]
   The number and percentage of subjects who are pain free at 2 hours post treatment initiation (if rescue therapy was not used), in their first eligible treated migraine attack

Other Outcome Measures:

1. Number of Participants With Adverse Events [ Time Frame: From Enrollment (randomization) through study exit i.e. 70 days ]
   Safety of the study device following study treatment: Number and Rate of participates with Adverse events related or unrelated to the study device
2. The Change in Pseudo-continuous Pain Score From Baseline to 1-hour Post Treatment [ Time Frame: baseline to 1-hour post treatment ]
   as per the Statistical Considerations for Clinical Trials During the COVID-19 Public Health Emergency" June 2020 FDA Guidance, which states that a modifications to the definition and ascertainment of trial endpoints may be warranted to address the impact of COVID-19. A potential modification for a binary endpoint that is based on a continuous or ordinal measurement is by using the continuous or ordinal measurement as the endpoint. therefore, an additional analysis to the study end points , the migraine headache pain level was transformed into a numerical score (pseudo-continuous): "No pain"=0, "Mild"=1, "Moderate"=2, "Severe"=3. If rescue medication was used, the score after the rescue intake post-treatment are set to the baseline value. The change from baseline is compared between the study arms with an analysis of covariance model adjusted for site and baseline pain level.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects 18 years of age and older.
2. Subject meets the ICHD (International Classification of Headache Disorders)-3 (2018) diagnostic criteria for Migraine with or without aura.
3. Subject reports 1-6 Migraine attacks per month; other headaches no more than 6 days per month.
4. Subject is willing to and capable of complying with the specified study requirements, provided written Informed Consent, can complete the electronic diaries, and can be contacted by telephone.

Exclusion Criteria:

1. Subject having received Botox treatment in the head region in the prior 3 months.
2. Subject having received supraorbital or occipital nerve blocks in the prior month.
3. Past 6 months of chronic migraine, New Daily Persistent Headache, and chronic tension-type headache per ICHD-3 (2018) diagnostic criteria.
4. Current medication overuse headache.
5. Use of opioid medications in the prior 1 month.
6. Use of barbiturates in the prior 1 month.
7. Subject has >10 headache days per month
8. Implanted metal/shrapnel or electrical devices in the head (not including dental implants), a cardiac pacemaker or an implanted or wearable defibrillator.
9. Received parenteral infusions for migraine within the previous 2 weeks.
10. Subject has known uncontrolled epilepsy.
11. History of neurosurgical interventions
12. Subject with implanted neurostimulators, surgical clips (above the shoulder line) or any medical pumps.
13. Current drug abuse or alcoholism.
14. Subject is participating in any other clinical study.
15. Skin lesion or inflammation at the region of the stimulating electrodes.
16. Personality or somatoform disorder.
17. Pregnancy or Lactation.
18. Women with child bearing potential without medically acceptable method of contraception (NOTE: Females of child bearing potential must have a negative pregnancy test).
19. Documented history of cerebrovascular event.
20. Subject with recent brain or facial trauma (occurred less than 3 months prior to this study).
21. Subject participated in a previous study with the Relivion device.
22. The subject does not have the basic cognitive and motor skills needed to operate a smartphone.
23. Subject with head circumference smaller than 51 centimeters or head circumference larger than 60 centimeters
24. Subject with other significant pain problem that in the opinion of the investigator may confound the study assessments.

Contacts and Locations

Locations

United States, Arizona

Clinical Research Consortium, an AMR company

Tempe, Arizona, United States, 85283

United States, Connecticut

Hartford HealthCare Headache Center

Hartford, Connecticut, United States, 06107

Yale School of Medicine

New Haven, Connecticut, United States, 06519

United States, Massachusetts

Regeneris Medical

North Attleboro, Massachusetts, United States, 02760

United States, Nevada

Clinical Research Consortium, an AMR company

Las Vegas, Nevada, United States, 89119

United States, New Hampshire

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States, 03756

Israel

Barzilai MC

Ashkelon, Israel

Hillel Yaffe Medical Center

Hadera, Israel

Sharei Zedek MC

Jerusalem, Israel

Macabi healtcenter services

Kfar Saba, Israel

Laniado MC

Netanya, Israel

Macabi healtcenter services

Ra'anana, Israel

Sponsors and Collaborators

Neurolief Ltd.

Investigators

• Principal Investigator: stewart J. Tepper, Dr.; Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

  Study Documents (Full-Text)

Documents provided by Neurolief Ltd.:

Study Protocol  [PDF] June 11, 2019

Statistical Analysis Plan  [PDF] August 31, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tepper SJ, Grosberg B, Daniel O, Kuruvilla DE, Vainstein G, Deutsch L, Sharon R. Migraine treatment with external concurrent occipital and trigeminal neurostimulation-A randomized controlled trial. Headache. 2022 Sep;62(8):989-1001. doi: 10.1111/head.14350. Epub 2022 Jun 24.

• Responsible Party: Neurolief Ltd.
• ClinicalTrials.gov Identifier: NCT03631550
• Other Study ID Numbers: SP-302 RIME
• First Posted: August 15, 2018
• Results First Posted: July 12, 2022
• Last Update Posted: September 22, 2022
• Last Verified: September 2022

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

Additional relevant MeSH terms:

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