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

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®)

Study Overview

• Status: Completed
• Conditions: Acute Migraine
• Intervention / Treatment: Device: Relivion active; Device: Relivion Sham

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 Type: Interventional
• Enrollment (Actual): 187
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Ashkelon, Israel
    • Barzilai MC
  • Hadera, Israel
    • Hillel Yaffe Medical Center
  • Jerusalem, Israel
    • Sharei Zedek MC
  • Kfar Saba, Israel
    • Macabi healtcenter services
  • Netanya, Israel
    • Laniado MC
  • Ra'anana, Israel
    • Macabi healtcenter services
• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Clinical Research Consortium, an AMR company
  • Connecticut
    • Hartford, Connecticut, United States, 06107
      • Hartford Healthcare Headache Center
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine
  • Massachusetts
    • North Attleboro, Massachusetts, United States, 02760
      • Regeneris Medical
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Clinical Research Consortium, an AMR company
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Reporting Reduction of Migraine Headache Pain at 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)	2 hours from treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Reporting Improvement in Their Most Bothersome Symptom (MBS) Other Than a Headache, 2 Hours Post-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 hours from treatment initiation
Proportion of Subjects Reporting Reduction of Migraine Headache Pain 1-hour Post 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	1 hour from treatment initiation
Proportion of Subjects Who Are Pain Free at 2 Hours Post 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	2 hours from treatment initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Safety of the study device following study treatment: Number and Rate of participates with Adverse events related or unrelated to the study device	From Enrollment (randomization) through study exit i.e. 70 days
The Change in Pseudo-continuous Pain Score From 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.	baseline to 1-hour post treatment

Collaborators and Investigators

• Sponsor: Neurolief Ltd.
• Investigators: Principal Investigator: stewart J. Tepper, Dr., Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2018
• Primary Completion (Actual): August 4, 2020
• Study Completion (Actual): August 4, 2020

Study Registration Dates

• First Submitted: August 13, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: SP-302 RIME

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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