Remote Electrical Neuromodulation for Acute Treatment of Migraine in Adolescents

Andrew D. Hershey MD, PhD, FAAN, FAHS; Tamar Lin PhD; Yaron Gruper MSc; Dagan Harris PhD; Alon Ironi MSEE; Thomas Berk MD; Christina L. Szperka MD, MSCE; Frank Berenson MD, FAHS

Disclosures

Headache. 2021;61(2):310-317. 

In This Article

Results

Participants

This study was conducted from October 9, 2019 to May 24, 2020 (completion of the treatment phase). A total of 60 participants were enrolled, of which 1 participant was lost to follow-up during the run-in phase, and 14 completed the run-in but were not eligible to continue according to protocol specifications (Figure 1). Of the 14 participants who failed to meet the run-in criteria, 12 participants were ineligible due to insufficient number of attacks (less than three attacks), and 2 participants were ineligible due to noncompliance with migraine attack diary reporting requirements.

Figure 1.

Participants disposition

Among the 45 participants who entered the treatment phase, all completed at least one treatment (the training treatment) and 39 participants completed at least one additional treatment with baseline and 2-hour data following the training treatment, forming the final analysis set (2 participants had missing data at 2 hours, three participants did not have migraine headaches and one participant was a lost to follow-up; Figure 1).

The demographic and clinical characteristics of the participants (Table 1) and the characteristics of treated migraine headaches were comparable to those reported in previous studies of migraine in adolescents.[22,23]

Treated Migraine Headaches

A total of 159 qualifying migraine headaches were treated with the device for which pain data was recorded at baseline and at 2 hours (average of 3.5 treatments per participant). Pain severity of treated migraine headaches was mostly moderate (48% [77/159]). Generally, the characteristics of treated migraine headaches were comparable to those reported in previous migraine studies in adolescents.[22] The characteristics of the test treatments are presented in Table 2.

Safety and Tolerability

Safety analyses were performed on all 45 participants who used the device at least once. 10 participants (22%; CI95% 11%–37%) reported at least one adverse event. There was one mild device-related adverse event reported (2%; CI95% 0.06%–11%) in which a temporary feeling of pain in the arm was felt but resolved after the treatment without requiring intervention. The other adverse events which were deemed unrelated to the device included common cold (1), chest congestion (2), influenza (2), leg pain (1), streptococcus pharyngitis (1), upper respiratory infection (1), and worsened migraine (1). There were no device-related serious adverse events and none of the participants withdrew from the study due to device-related adverse events.

Efficacy Outcomes

Pain relief and pain-free at 2 hours were achieved by 71% (28/39; CI95% 55%–85%) and 35% (14/39; CI95% 21%–52%) participants, respectively (Table 3 and Figure 2). In a sensitivity analysis assuming all treatments with missing pain level data were considered failures, pain relief was achieved by 68% (28/41; CI95% 51%–81%) of the participants.

Figure 2.

Pain outcomes. (A) Percentage of participants achieving pain relief and pain-free at 2 hours response in at least 50% of treated attacks. (B) Percentage of participants achieving sustained pain relief at 24 hours and sustained pain-free response in at least 50% of treated attacks. The error bars represent 95% confidence intervals

Pain relief was sustained for 24 hours in 90% (20/22; CI95% 70%–98%) of the participants, and pain freedom was sustained for 24 hours in 90% (10/11; CI95% 58%–99%) of the participants (only subjects achieving relief/freedom at 2 hours were included in the analyses; six participants who achieved pain relief at 2 hours did not report pain level at 24 hours and were excluded from the sustained pain relief analysis and four participants who achieved pain freedom at 2 hours did not report pain level at 24 hours and were excluded from the sustained pain freedom analysis). A sensitivity analysis assuming all treatments with missing pain level data at 24 hours had return of pain (i.e., considered failures) further indicated a favorable sustained response; sustained pain relief was achieved by 71% (20/28; CI95% 51%–87%) of the participants and sustained pain freedom was achieved by 67% (10/15; CI95% 38%–88%).

Nausea, photophobia, and phonophobia disappeared at 2 hours in 54% (12/22; CI95% 32%–75%), 41.9% (13/31; CI95% 24%–60%), and 40% (10/25; CI95% 21%–61%) participants, respectively. We also evaluated the disappearance of at least one associated symptom of nausea and/or vomiting, photophobia, and phonophobia (defined as disappearance of at least one symptom at 2 hours which was present at baseline. 66% (25/38; CI95% 49%–80%) of the participants experienced disappearance of at least one of the associated symptoms in the test treatment (1 participant who did not have any of the symptoms at baseline was excluded from the analysis). Furthermore, 69% (23/33; CI95% 51%–84%) participants experienced improvement in functional ability at 2 hours (only participants with functional disability at baseline were included in the analysis).

Two participants (5%) used medication within 2 hours of the test treatment, demonstrating compliance rate of 94%. Additionally, one participant (2%) started the test treatment over 60 minutes of attack onset, demonstrating compliance rate of 97% to treat early.

An additional highly important aspect of acute treatments of migraine from a clinical standpoint is efficacy across multiple attacks. Accordingly, to derive more stable estimates of long-term response to the treatment, a consistency analysis was conducted (excluding the training treatment). A total of 110 treatments (excluding the training treatment) were performed by the 39 participants (average of 2.8 treatments per participant) and included in the consistency analysis. This analysis demonstrated that 66% (26/39; CI95% 49%–80%) of the participants experienced pain relief in at least 50% of their treated attacks, and 33% (13/39; CI95% 19%–50%) of the participants experienced pain-free in at least 50% of their treated attacks (Table 3 and Figure 2).

Improvement in Migraine-related Disability

Forty-two participants who completed the questionnaire both at baseline and at the end of treatment phase were included in the analysis. The change between the PedMIDAS scores at enrollment (37.1 [30.4]) and the end of the treatment phase (18.5 [26.8]) was 18.6 (23.4) with an interquartile range of 27.5.

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