Randomized, Placebo-Controlled Pilot Trial of a Novel, Noninvasive EEG-Based Intervention, HIRREM, for Alleviation of Episodic Migraine

C.H. Tegeler1, C.L. Tegeler1, S.R. Kumar1, D.P. Turner1, L. Gerdes2, S.W. Lee2, T.T. Houle1
1

Wake Forest School of Medicine, Winston Salem, NC, USA; 2Brain State Technologies, LLC, Scottsdale, AZ, USA. Objectives: To pilot test high-resolution, relational, resonance-based electroencephalic mirroring (HIRREMTM) for reduction of headache (HA) frequency and severity in episodic migraine (MI) and to estimate effect sizes for use in a larger trial. Background: Studies have identified altered proportionation of power across broad-band bins of the EEG frequency spectrum in MI. HIRREM is a novel, noninvasive technology designed to facilitate relaxation and auto-calibration of neural oscillations. HIRREM involves collection of EEG data from 2-channel recordings, analysis of the data at high spectral resolutions (0.001 hertz), and delivery of auditory tones for resonance in near real time with dynamically varying dominant EEG frequencies. Methods: Sixty-three subjects were screened, 33 enrolled, and 30 (16 HIRREM, 14 placebo; mean age 51 11, 26 women) completed an IRB-approved, randomized, single-blind, placebocontrolled, pilot trial. Individuals assigned to active HIRREM underwent a series of 90-minute sessions (mean 10.0, range 8-12) over a mean of 2.7 weeks (range 1-5), each of which consisted of listening to near real time auditory feedback derived from their own dynamically varying EEG activity. Individuals assigned to placebo had a comparable number of visits but listened to randomly generated musical tones. Subjects maintained a daily HA diary prior to undergoing intervention (2 weeks), during intervention, and for 2 months afterward. Primary outcome was defined as a joint distribution of HA frequency and intensity during the postintervention follow up period. Analysis used a mixed effects, mixed distributions model to predict probability of an attack, and, when present, intensity of the attack. Using random effects, the model considers the hierarchical data structure of multiple diary days nested within a person. Results: Three subjects had malfunctions in electronic daily diary tools and were excluded from analysis. Before the intervention, the HIRREM group tended to have greater likelihood of HA compared to placebo, OR 1.56 (95% CI: 0.97 to 2.53, p = 0.064). However, during the postintervention period, the HIRREM group had a reduction in the likelihood of experiencing headache compared to controls, OR 0.74 (95% CI: 0.55 to 1.03, p = 0.077). This clinically meaningful effect size did not reach statistical significance in this pilot sample. No adverse events occurred. A comparable number of subjects in each group (50%) guessed that they received active HIRREM. Conclusions: In this pilot trial, a promising effect size for reduction in headache frequency was observed for the HIRREM intervention beyond that observed for a placebo condition. The effect size associated with HIRREM as well as its safety and lack of side effects suggest that larger controlled trials are warranted.