Clinical trial NCT04992897: Real-world Data Analysis of REN Treatment in Migraine Patients
Official title: Real-world Analysis of Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Migraine
Keywords: Migraine
headache
REN
Nerivio
Lead sponsor: Theranica
Sponsor class: INDUSTRY
Collaborators: name: Georgetown University
name: Mayo Clinic
First posted: 2021-08-05
Enrollment: 12151
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: REN users across the United States who used Nerivio between October 1st, 2019, and May 24th, 2021.

Brief summary: Data analysis concerning four sets of metrics: A. Per-treatment patterns of REN use as a standalone treatment vs. in combination with medications. B. Per-user Intra-individual consistency of efficacy across multiple treatments (consistency defined as a response to treatment in at least 50% of treatments). C. Distribution of treatment intensity among users (the electroceutical equivalent to treatment dose). D. Prevalence and severity of adverse events.

Detailed description: The REN device The REN device is a wearable device applied to the upper arm and stimulates C and Aδ noxious fibers using a modulated, symmetrical, biphasic, square pulse with a pulse width of 400 μs, modulated frequency of 100-120 Hz, and up to 40 mA output current which can be adjusted by the patient.

Data collection As part of the sign-up process to the Nerivio app, all patients accept the terms of use which specify that providing personal information is done of their own free will, and that their de-identified data may be used for research purposes. Users were not obligated to provide personal information and could treat without providing any feedback. The app includes a secured, personal migraine diary, which enables patients to record and track their migraines and other headaches. At the beginning of each treatment, and again 2 hours after the start of treatment, patients are prompted to record their symptoms, including pain level (none, mild, moderate, severe), functional disability ('No limitation, 'Some limitation', 'Moderate limitation, 'Severe limitation), and indication of which medications, if any, were taken within that 2-hour time window.

Dataset Real-world data of REN treatments collected from patients across the United States who used the REN device.

'Treatment' defined as a REN treatment of at least 20 minutes (the nominal duration is 45 minutes).

'Evaluable treatment' defined as a treatment in which pain levels were reported at baseline and post 2 hours.

Inclusion criteria for each of the different metrics:

A. REN-medication combinations: all evaluable treatments. B. Consistent efficacy: all users that performed at least 2 evaluable treatments. In order to isolate the effect of REN treatments, this dataset considered only treatments where REN was used as a standalone treatment.

C. Intensity stability: all treatments. D. Safety: all reported adverse events (AEs) within the time period.

Outcome measures

Respectively, outcome measures:

A. REN-Medication combinations (prevalence \& efficacy):

Medication intake outcomes calculated based on the 2h post-treatment report and comprised of the percentage of treatments in which no rescue medications were used, treatments in which OTC medications were taken, treatments in which triptans were taken, treatments in which other prescription medications were taken, and treatments in which medication intake status was not reported. OTC included acetaminophen, NSAIDs, and combinations of the two, with or without caffeine.

Efficacy outcomes calculated based on the baseline and post-2h reports and comprised of:

(i) consistency of pain relief (decrease in headache from moderate or severe at baseline to mild or no pain); (ii) consistency of pain-freedom (decrease in headache from mild, moderate, or severe at baseline to no pain); (iii) Consistency of improvement in function (improvement in at least one grade between baseline and 2 hours); and (iv) consistency of return to normal function (no functional disability at 2 hours).

B. Consistent efficacy:

Consistency defined as a response of a patient to the treatment in at least 50% of their treated attacks, and calculated for the four efficacy outcomes: (i) consistency of pain relief (ii) consistency of pain-freedom (iii) consistency of improvement in function; and (iv) consistency of return to normal function.

C. Treatment intensity:

The mean intensity of the stimulation collected for all treatments that were 20 minutes or longer, which were performed within the study's time window.

D. Safety:

All adverse events that were reported within the study's period, the following information provided: number of device-related AEs, percentage of the device-related AEs that were mild, moderate, and severe, and percentage of AEs that were serious vs. not serious.

Eligibility criteria: Inclusion Criteria:

REN users in the U.S.

Exclusion Criteria:

Cohort 1 REN treatments that were shorter than 20 minutes or did not have a report of pain level.

Cohort 2 Treatments in which medications were taken within 2 hours from REN treatment. Users that had less than 2 REN treatments.

Cohort 3 REN treatments that were shorter than 20 minutes

Cohort 4 All REN sessions, regardless of duration or medication intake.

Primary outcomes:
measure: REN-medication combinations- prevalence
timeFrame: 2 hours from treatment onset
measure: REN-medication combinations- efficacy of the combinations
timeFrame: 2 hours from treatment onset
measure: percentage of users that achieve consistency of efficacy
timeFrame: 2 hours from treatment onset
measure: Treatment intensity distribution
timeFrame: 20 minutes from treatment onset
measure: Safety (number of users reporting device/treatment-related adverse events)
timeFrame: 20 months
Secondary outcomes:
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Theranica USA Inc
state: New Jersey
city: Netanya
country: Israel
facility: Theranica Bio-Electronics
Study officials:
References:
citation: Yarnitsky D, Dodick DW, Grosberg BM, Burstein R, Ironi A, Harris D, Lin T, Silberstein SD. Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Headache. 2019 Sep;59(8):1240-1252. doi: 10.1111/head.13551. Epub 2019 May 9.
citation: Tepper SJ, Lin T, Montal T, Ironi A, Dougherty C. Real-world Experience with Remote Electrical Neuromodulation in the Acute Treatment of Migraine. Pain Med. 2020 Dec 25;21(12):3522-3529. doi: 10.1093/pm/pnaa299.
citation: Hershey AD, Lin T, Gruper Y, Harris D, Ironi A, Berk T, Szperka CL, Berenson F. Remote electrical neuromodulation for acute treatment of migraine in adolescents. Headache. 2021 Feb;61(2):310-317. doi: 10.1111/head.14042. Epub 2020 Dec 21.
citation: Nierenburg H, Vieira JR, Lev N, Lin T, Harris D, Vizel M, Ironi A, Lewis B, Wright P. Remote Electrical Neuromodulation for the Acute Treatment of Migraine in Patients with Chronic Migraine: An Open-Label Pilot Study. Pain Ther. 2020 Dec;9(2):531-543. doi: 10.1007/s40122-020-00185-1. Epub 2020 Jul 9.
citation: Rapoport AM, Lin T. Device profile of the Nerivio for acute migraine treatment: overview of its efficacy and safety. Expert Rev Med Devices. 2019 Dec;16(12):1017-1023. doi: 10.1080/17434440.2019.1695599. Epub 2019 Nov 25.
citation: Marmura MJ, Lin T, Harris D, Ironi A, Rosen NL. Incorporating Remote Electrical Neuromodulation (REN) Into Usual Care Reduces Acute Migraine Medication Use: An Open-Label Extension Study. Front Neurol. 2020 Apr 7;11:226. doi: 10.3389/fneur.2020.00226. eCollection 2020.