Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

David Yarnitsky, David William Dodick, Brian M. Grosberg, Rami Burstein, Alon Ironi, Dagan Harris, Tamar Lin, Stephen D. Silberstein

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

OBJECTIVE: To assess the efficacy and safety of a remote electrical neuromodulation (REN) device for the acute treatment of migraine. BACKGROUND: There is a significant unmet need for novel effective well-tolerated acute migraine treatments. REN is a novel acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation - an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. A recent pilot study showed that REN can significantly reduce headache. We have conducted a randomized, double-blind, sham-controlled study to further evaluate the efficacy and safety of REN for the acute treatment of migraine. METHODS: This was a randomized, double-blind, sham-controlled, multicenter study conducted at 7 sites in the United States and 5 sites in Israel. Two hundred and fifty-two adults meeting the International Classification of Headache Disorders criteria for migraine with 2-8 migraine headaches per month were randomized in a 1:1 ratio to active or sham stimulation. A smartphone-controlled wireless device was applied for 30-45 minutes on the upper arm within 1 hour of attack onset; electrical stimulation was at a perceptible but non-painful intensity level. Migraine pain levels were recorded at baseline, 2, and 48 hours post-treatment. Most bothersome symptoms (MBS) were also recorded. The primary efficacy endpoint was the proportion of participants achieving pain relief at 2 hours post-treatment (improvement from severe or moderate pain to mild or none, or from mild pain to none). Relief of MBS and pain-free at 2 hours were key secondary endpoints. RESULTS: Active stimulation was more effective than sham stimulation in achieving pain relief (66.7% [66/99] vs 38.8% [40/103]; therapeutic gain of 27.9% [CI95% , 15.6-40.2]; P < .0001), pain-free (37.4% vs 18.4%, P = .003), and MBS relief (46.3% vs 22.2%, P = .0008) at 2 hours post-treatment. The pain relief and pain-free superiority of the active treatment was sustained 48 hours post-treatment. The incidence of device-related adverse events was low and similar between treatment groups (4.8% [6/126] vs 2.4% [3/126], P = .499). CONCLUSIONS: REN provides superior clinically meaningful relief of migraine pain and MBS compared to placebo, offering a safe and effective non-pharmacological alternative for acute migraine treatment.

Original languageEnglish (US)
Pages (from-to)1240-1252
Number of pages13
JournalHeadache
Volume59
Issue number8
DOIs
StatePublished - Sep 1 2019

Fingerprint

Migraine Disorders
Multicenter Studies
Placebos
Pain
Therapeutics
Equipment and Supplies
Arm
Safety
Body Regions
Headache Disorders
Israel
Peripheral Nerves
Electric Stimulation
Headache
Analgesics

Keywords

  • conditioned pain modulation
  • headache
  • migraine
  • neuromodulation
  • non-pharmacological treatment
  • remote electrical neuromodulation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Remote Electrical Neuromodulation (REN) Relieves Acute Migraine : A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. / Yarnitsky, David; Dodick, David William; Grosberg, Brian M.; Burstein, Rami; Ironi, Alon; Harris, Dagan; Lin, Tamar; Silberstein, Stephen D.

In: Headache, Vol. 59, No. 8, 01.09.2019, p. 1240-1252.

Research output: Contribution to journalArticle

Yarnitsky, D, Dodick, DW, Grosberg, BM, Burstein, R, Ironi, A, Harris, D, Lin, T & Silberstein, SD 2019, 'Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial', Headache, vol. 59, no. 8, pp. 1240-1252. https://doi.org/10.1111/head.13551
Yarnitsky, David ; Dodick, David William ; Grosberg, Brian M. ; Burstein, Rami ; Ironi, Alon ; Harris, Dagan ; Lin, Tamar ; Silberstein, Stephen D. / Remote Electrical Neuromodulation (REN) Relieves Acute Migraine : A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. In: Headache. 2019 ; Vol. 59, No. 8. pp. 1240-1252.
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abstract = "OBJECTIVE: To assess the efficacy and safety of a remote electrical neuromodulation (REN) device for the acute treatment of migraine. BACKGROUND: There is a significant unmet need for novel effective well-tolerated acute migraine treatments. REN is a novel acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation - an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. A recent pilot study showed that REN can significantly reduce headache. We have conducted a randomized, double-blind, sham-controlled study to further evaluate the efficacy and safety of REN for the acute treatment of migraine. METHODS: This was a randomized, double-blind, sham-controlled, multicenter study conducted at 7 sites in the United States and 5 sites in Israel. Two hundred and fifty-two adults meeting the International Classification of Headache Disorders criteria for migraine with 2-8 migraine headaches per month were randomized in a 1:1 ratio to active or sham stimulation. A smartphone-controlled wireless device was applied for 30-45 minutes on the upper arm within 1 hour of attack onset; electrical stimulation was at a perceptible but non-painful intensity level. Migraine pain levels were recorded at baseline, 2, and 48 hours post-treatment. Most bothersome symptoms (MBS) were also recorded. The primary efficacy endpoint was the proportion of participants achieving pain relief at 2 hours post-treatment (improvement from severe or moderate pain to mild or none, or from mild pain to none). Relief of MBS and pain-free at 2 hours were key secondary endpoints. RESULTS: Active stimulation was more effective than sham stimulation in achieving pain relief (66.7{\%} [66/99] vs 38.8{\%} [40/103]; therapeutic gain of 27.9{\%} [CI95{\%} , 15.6-40.2]; P < .0001), pain-free (37.4{\%} vs 18.4{\%}, P = .003), and MBS relief (46.3{\%} vs 22.2{\%}, P = .0008) at 2 hours post-treatment. The pain relief and pain-free superiority of the active treatment was sustained 48 hours post-treatment. The incidence of device-related adverse events was low and similar between treatment groups (4.8{\%} [6/126] vs 2.4{\%} [3/126], P = .499). CONCLUSIONS: REN provides superior clinically meaningful relief of migraine pain and MBS compared to placebo, offering a safe and effective non-pharmacological alternative for acute migraine treatment.",
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AU - Dodick, David William

AU - Grosberg, Brian M.

AU - Burstein, Rami

AU - Ironi, Alon

AU - Harris, Dagan

AU - Lin, Tamar

AU - Silberstein, Stephen D.

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N2 - OBJECTIVE: To assess the efficacy and safety of a remote electrical neuromodulation (REN) device for the acute treatment of migraine. BACKGROUND: There is a significant unmet need for novel effective well-tolerated acute migraine treatments. REN is a novel acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation - an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. A recent pilot study showed that REN can significantly reduce headache. We have conducted a randomized, double-blind, sham-controlled study to further evaluate the efficacy and safety of REN for the acute treatment of migraine. METHODS: This was a randomized, double-blind, sham-controlled, multicenter study conducted at 7 sites in the United States and 5 sites in Israel. Two hundred and fifty-two adults meeting the International Classification of Headache Disorders criteria for migraine with 2-8 migraine headaches per month were randomized in a 1:1 ratio to active or sham stimulation. A smartphone-controlled wireless device was applied for 30-45 minutes on the upper arm within 1 hour of attack onset; electrical stimulation was at a perceptible but non-painful intensity level. Migraine pain levels were recorded at baseline, 2, and 48 hours post-treatment. Most bothersome symptoms (MBS) were also recorded. The primary efficacy endpoint was the proportion of participants achieving pain relief at 2 hours post-treatment (improvement from severe or moderate pain to mild or none, or from mild pain to none). Relief of MBS and pain-free at 2 hours were key secondary endpoints. RESULTS: Active stimulation was more effective than sham stimulation in achieving pain relief (66.7% [66/99] vs 38.8% [40/103]; therapeutic gain of 27.9% [CI95% , 15.6-40.2]; P < .0001), pain-free (37.4% vs 18.4%, P = .003), and MBS relief (46.3% vs 22.2%, P = .0008) at 2 hours post-treatment. The pain relief and pain-free superiority of the active treatment was sustained 48 hours post-treatment. The incidence of device-related adverse events was low and similar between treatment groups (4.8% [6/126] vs 2.4% [3/126], P = .499). CONCLUSIONS: REN provides superior clinically meaningful relief of migraine pain and MBS compared to placebo, offering a safe and effective non-pharmacological alternative for acute migraine treatment.

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KW - conditioned pain modulation

KW - headache

KW - migraine

KW - neuromodulation

KW - non-pharmacological treatment

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