An interventional study of Active Remote Electrical Neuromodulation and Sham Remote Electrical Neuromodulation in Migraine and Migraine Headache, sponsored by University of Calgary. Not yet recruiting at 1 site in Canada. Open to participants aged 8 Years to 18 Years. Per ClinicalTrials.gov, last updated 2026-08-19.
Sponsored by University of Calgary · Not applicable, Interventional, and Treatment
Background \& Rationale:
One in ten Canadian youth have migraine, a disabling neurological disease that is more common in females and characterized by moderate-severe disabling headaches. Migraine attacks occur in a cycle that begins with a prodromal phase, followed by aura, a pain phase (headache), and finally a postdrome phase when the pain is resolved but other symptoms persist. The prodrome is recognized by \~90% of all youth with migraine, occurs up to 24 hours before headache onset, and consists of a variety of symptoms including, but not limited to, food cravings, fatigue, yawning, mood changes, and sensory hypersensitivity (e.g., light sensitivity). Prodromal symptoms are disabling and frequently graded as moderate to severe. All acute migraine treatments for youth have been studied for use in the pain phase, with the greatest treatment success early in this phase. Unfortunately, only \~1/3 of youth achieve pain freedom within two hours. Recently, a groundbreaking trial found that treatment during the prodrome could prevent the pain phase, although prodromal treatment does not exist for youth.
In considering the most innovative, safe, and patient-centered prodromal intervention, remote electrical neuromodulation (REN) is the obvious choice. The investigator's engagement with 175 youth with migraine and their caregivers shows that REN is preferred when pill-based interventions are ineffective or impractical. REN has none of the limitations of pill-based prodromal treatment. The REN device is wearable, battery-operated, worn on the upper arm, and controlled wirelessly by a smartphone application. REN electrically stimulates sensory nerves in the arm below their perceived pain thresholds, but above their depolarization thresholds, to induce a conditioned pain modulation response in the brain to modulate incoming migraine pain signals.
Clinical trial and observational studies in youth with migraine have shown REN's safety and efficacy for home-based treatment during the pain phase and led the FDA to clear its use in youth >8 years. In the adolescent trial, 71% of participants had pain relief at two hours, there were no serious adverse events (AE), and only one device-related AE (transient arm pain) occurred. Also, emerging data show that adults with migraine in the prodrome phase display pain facilitation due to a deficit in pain modulation. Thus, REN's mechanism of action is likely to be more effective during the prodrome vs. the pain phase as it can "turn on" deficient pain modulatory areas earlier when they are most impaired.
Research Question \& Objectives:
The investigators aim to determine the feasibility of implementing REN treatment during the prodrome to prevent migraine pain in youth with migraine, and hypothesize that:
The following feasibility and acceptability outcomes will be measured:
All secondary outcomes will be reported descriptively, and adverse events will be recorded and reported.
Methods:
This study will be a pilot randomized, single centre, double-blind, parallel group, sham-controlled trial comparing active to sham REN for the prevention of headache within 24 hours of treating prodromal symptoms in youth with migraine. Participants will be recruited from headache and neurology clinics at the Alberta Children's Hospital.
Eligible and consenting participants will complete an intake visit and enter a 60-day screening period where they will complete electronic daily diaries to determine prodrome or headache occurrence and features. Participants with 3-28 qualifying prodromes during screening, where >75% are followed by a headache within 6 hours, will be randomized 1:1 to treat one qualifying prodrome with active or sham REN over a 60-day treatment period. Participants will be trained on device use and will be instructed to not use any co-interventions during the qualifying prodrome; if headache onsets after the prodrome, participants will be instructed to use their typical acute treatment. During the treated prodrome, a survey will determine the presence, type, and number of prodromal symptoms. Surveys at 2, 24, and 48 hours post-treatment will record the presence or absence of headache, its characteristics, and AEs.
The randomization sequence will be prepared by a biostatistician and will follow randomly ordered blocks of four and six, with variable block sizes. Only research pharmacists will have access to this sequence to prepare consecutively numbered blinded and matched study kits. These kits will contain a restricted mobile phone with only the REN software application pre-installed.
1,657 studies on the registry are indexed under Migraine Disorders; 339 are open to participants now.
This study's planned enrollment of 30 is below the median of 80 across 1,269 interventional studies indexed under Migraine Disorders.
Browse Migraine Disorders studies →University of Calgary is the lead sponsor of 703 studies on the registry; 196 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 2 (20%) have results posted.
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To proceed past the 60-day screening period to randomization, participants will need to report 3-28 qualifying prodrome events with >75% of these events followed by a headache within 6 hours.
Exclusion Criteria:
45 minutes of a modulated symmetrical biphasic square electrical pulse, modulated frequency of 100-120 Hz, pulse width of 400 µs, maximum of 40 mA, which modulates the pain response in the brain using conditioned pain modulation to trigger an analgesic effect.
Device: Active Remote Electrical Neuromodulation
45 minutes of modulated symmetrical biphasic square electrical pulse, modulated frequency of \~0.083 Hz and a modulated pulse width of 40-550 µs. The sham device produces sensations comparable to the active device, appears identical to the active device, is also controlled wirelessly by a smartphone application, but uses lower stimulation parameters which were ineffective in adult trials.
Device: Sham Remote Electrical Neuromodulation
The REN device modulates the pain response in the brain using conditioned pain modulation to trigger an analgesic effect. This mechanism is achieved by electrically stimulating the C and Aδ nociceptive sensory nerves in the upper arm, just below the perceived pain threshold and above the depolarization threshold. Precise activation of these sensory nerves further triggers ascending pain pathways within the spinothalamic tract and brain stem. These pathways further activate descending pain inhibitory pathways within the brain stem to modulate incoming pain signals and produce an analgesic effect. The active REN device involves 45 minutes of a modulated symmetrical biphasic square electrical pulse, modulated frequency of 100-120 Hz, pulse width of 400 µs, maximum of 40 mA, which modulates the pain response in the brain using conditioned pain modulation to trigger an analgesic effect.
Also known as: REN
The sham REN device produces sensations comparable to the active REN device, appears identical to the active REN device, is also controlled wirelessly by a smartphone application, but uses lower stimulation parameters which were ineffective in adult trials. The sham REN device involves 45 minutes of modulated symmetrical biphasic square electrical pulse, modulated frequency of \~0.083 Hz and a modulated pulse width of 40-550 µs.
Feasibility - Proportion of Youth Enrolled Into Study
Proportion of eligible youth enrolled into screening period (target=50%).
Time frame: From enrollment to completion of the feedback form (between 60 and 120 days later).
Feasibility - Proportion of Participants Randomized to Study Treatment
Proportion of youth enrolled into screening period subsequently randomized (target=33%).
Time frame: From enrollment to completion of the feedback form (between 60 and 120 days later).
Feasibility - Proportion of Participants Using REN Treatment
Proportion of randomized youth treating a qualifying prodrome event (target=80%).
Time frame: From enrollment to completion of the feedback form (between 60 and 120 days later).
Study Acceptability Based on Participant Feedback
Participant feedback will be assessed based on the completion of multiple choice and free text items in a feedback form. Multiple choice responses will be "Strongly Disagree", "Disagree", "Neutral", "Agree", and "Strongly Agree", with "Agree" and "Strongly Agree" suggesting the study is acceptable to participants. Multiple choices items will be from previously published work (PubMed ID: 27390769). Free text responses will be reviewed to determine overall positive or acceptable aspects of the study and negative or not acceptable aspects of the study.
Time frame: 60 to 120 days after successful enrollment.
Effect Size Estimate
The main outcome that we will obtain an effect size estimate for will be the proportion of participants with absence of moderate-severe headache within 24 hours of prodromal treatment. All secondary outcomes will be reported descriptively, with a focus on describing the prevalence and consistency of prodromal symptoms as reported for the adult trial. For headache, pain severity will be measured using the 11-point pain numerical rating scale where 0 = no pain and 10 = the most intense pain imaginable (where a higher rating equals worse pain and worse outcomes). To align with International Headache Society and FDA guidelines for migraine trials, we will also use the 4-point pain severity scale (0=none, 1=mild, 2=moderate, 3=severe; higher ratings equal worse severity and outcomes), and participants will be asked about their most bothersome migraine associated symptom, and whether it is present or not.
Time frame: From enrollment to completion of the feedback form (between 60 and 120 days later).
Plan to share: No — Only aggregate data will be reported and there are currently no plans to share the individual participant data outside of the research team.
Start is estimated for Oct 2026; primary completion for Oct 2027, 12 months later.
Of 309 non-industry interventional studies with no phase under Migraine Disorders, half reached primary completion within 17 months of starting (the median), counting those still running; a quarter within 8 and three quarters within 36. This study's planned 12 months is below that.
Counting every sponsor, half of 358 studies reached it within 15 months; a quarter within 7 and three quarters within 34.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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