A Pilot Clinical Trial of a New Neuromodulation Device for Acute Attacks of Migraine in Children and Adolescents

A Pilot Clinical Trial of a New Neuromodulation Device for Acute Attacks of Migraine in Children and Adolescents

Brief Summary:
Migraine is a neurological disease characterized by severe and recurrent headaches. Children and adolescents with migraine often present to the emergency department (ED) with acute attacks, where migraine accounts for up to ~30% of all pediatric ED visits for headache. Based on the limited evidence, many centers have adopted protocols whereby children and adolescents who visit the ED with acute attacks of migraine are treated with an IV neuroleptic (metoclopramide or prochlorperazine) and an IV non-steroidal anti-inflammatory (ketorolac). This combination of interventions is largely considered to be standard of care despite no rigorous evidence to support this practice. Side effect rates with the neuroleptics (metoclopramide or prochlorperazine) are considerable, and IV catheters are associated with high adverse event and failure rates in children and adolescents. Therefore, the current standard of care for managing children and adolescents visiting the ED with acute attacks of migraine poses concern to patients and is associated with significant pain and frequent side effects.

Emerging neuromodulation devices show promise for expanding acute treatment options. Over the past few years, there has been a growth in research investigating the efficacy and safety of non-invasive neuromodulation, which delivers electrical or magnetic stimulation to nerves or neural tissue, for the management of acute attacks of migraine. At present, there are 3 commercially available, non-invasive neuromodulation devices that effectively and safely treat acute attacks of migraine in adults. Because none of these devices have a high level evidence in children, adolescents, nor in the ED setting, there is clinical equipoise as to which device would be most appropriate to study for treating children and adolescents visiting the ED with acute attacks. Throughout our patient engagement work, children and adolescents with migraine have identified that they are interested in trying remote electrical neuromodulation for treating migraine attacks in the ED.

The investigators propose a pilot randomized controlled trial (RCT) that will determine the feasibility and acceptability of executing a phase III RCT, in which children and adolescents visiting the ED with acute attacks of migraine will be randomized to REN or standard of care IV treatment, and then crossed over to the other treatment arm if the initial intervention is not effective.

Detailed Description:
One in ten Canadian children and adolescents suffer from migraine, and visits to the pediatric emergency department (ED) for acute attacks are common, with over 2,500 annual visits in Alberta alone. Evidence-based acute management options for children and adolescents presenting to the ED with acute attacks of migraine are limited. The current standard of care, which comprises a combination of a neuroleptic (metoclopramide) and a non-steroidal anti-inflammatory (ketorolac), has a low level of evidence and is administered through an intravenous (IV) cannula. However, at least half of children and adolescents presenting to the ED with acute attacks of migraine would prefer to avoid an IV, and these standard of care migraine interventions have substantial side effects and costs. The Nerivio remote electrical neuromodulation (REN) device is a novel, non-invasive, wearable REN device that is applied to the arm using an armband and wirelessly controlled by a smartphone software application. REN has established efficacy and safety for the treatment of acute attacks of migraine in adults, and preliminary open-label efficacy and safety data for use in adolescents. Through user engagement efforts, the investigators have identified that children and adolescents with migraine and ED providers are interested in trying REN to treat refractory acute attacks in the ED.

The investigators are proposing a pilot randomized controlled trial (RCT) that will aim to determine the feasibility and acceptability of implementing a phase III RCT, in which children and adolescents visiting the ED with acute attacks of migraine will be randomized to REN, or to standard of care IV treatment in a double-dummy crossover design. Participants will be crossed over to the other treatment arm if the initial intervention is not effective. The objectives of the investigators are:
1. To determine the feasibility of comparing REN to the standard of care IV intervention (i.e., a combination of metoclopramide and ketorolac) for the treatment of children and adolescents visiting the ED with acute attacks of migraine.
2. To determine the acceptability of the study design and of using REN to treat children and adolescents visiting the ED with acute attacks of migraine.
3. To gather preliminary efficacy and safety data on the use of REN to treat children and adolescents visiting the ED with acute attacks of migraine (for both the initial assigned intervention and the crossover intervention where applicable).

The investigators propose to carry out a pilot RCT to determine the feasibility and acceptability of implementing a double-dummy, crossover RCT protocol. In this pilot study, children and adolescents visiting the ED with acute attacks of migraine will be randomized to initially receive either REN or standard of care IV treatment (i.e. a combination of metoclopramide and ketorolac). Each group will also receive a blinded control (either normal saline through the IV for the REN group, or sham stimulation for the standard of care IV group). Consenting participants will be randomized at a 1:1 ratio to either REN or standard of care IV treatment. The allocation sequence will be sent to the research pharmacy and will not be accessible to anyone involved in the study or patient care. The REN group will receive active stimulation and normal saline placebo that will appear identical in appearance and volume to the medications given to the comparison group. The comparison group will receive a combination of pharmaceutical interventions that are considered to be the standard of care for treating children and adolescents visiting the ED with migraine: IV metoclopramide and IV ketorolac. The comparison group will also receive sham stimulation that will be low enough that it cannot induce conditioned pain modulation, the mechanism of action of REN, but it will be perceptible and similar to the sensation induced by the REN device. Stimulation for both groups occurs over 45 minutes. Participants will be assessed 120 minutes following the initial intervention and will be crossed over to the other treatment arm if the initial intervention is not effective. Efficacy and safety outcomes will be measured at baseline, 60 minutes, and 120 minutes (for both the initial and crossover study interventions as applicable), as well as 48 hours post-intervention.


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: The investigators will carry out a pilot randomized controlled trial (RCT) to determine the feasibility and acceptability of implementing a double-dummy, crossover RCT protocol.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Participants, research staff, and clinical staff, including the investigator, research assistant, research nurse, and attending physician, will remain blind to the study interventions.
Primary Purpose: Treatment
Official Title: A Pilot Clinical Trial of a New Neuromodulation Device for Acute Attacks of Migraine in Children and Adolescents Visiting the Emergency Department
Actual Study Start Date: February 22, 2022
Estimated Primary Completion Date: February 2025
Estimated Study Completion Date: February 2025

Arms:
- Standard-of-Care IV Group
- REN Group

View full details