RCT Demonstrating Effectiveness of TAN for Symptoms of Opioid Withdrawal

Introduction
According to the National Survey on Drug Use and Health, approximately 2.1 million Americans have severe opioid use disorder, resulting in a record 72,000 overdose deaths in 2017.¹⁻³ Treatment of opioid use disorder includes pharmacotherapies, psychosocial support, and behavioral modification.⁴⁻⁷ For many, opioid withdrawal is a rate-limiting factor in seeking treatment and sustaining recovery. Recently, neurostimulation approaches have earned scientific interest and demonstrated efficacy in treating/managing opioid withdrawal signs and symptoms.⁸⁻¹²

Methods
This was a double-blind, randomized, controlled study in which participants were randomized in a 1:1 ratio to one of two groups. Participants in the active tAN group received tAN immediately, whereas those in the delayed-active tAN had their therapy turned on after a 30-minute delay (inactive period). All participants were informed of their group assignment at the conclusion of the randomized, double-blind period, and all continued to receive active tAN throughout the five-day study. To demonstrate complete resolution of withdrawal, an intranasal naloxone challenge was performed at day 5 on subjects who were negative of opioids on urine drug screen.

The primary efficacy endpoint of this study was a successful mean percent change in clinical opiate withdrawal scale (COWS) score (defined as a ≥15% reduction13) from baseline to 60 minutes after the start of active tAN therapy. The distribution of COWS scores was examined for normality using a Shapiro Wilk test and tested using a one-sample t-test.

Results
After providing informed consent, 25 participants were randomized and received tAN therapy. Currently, 13 out of the 25 participants (52.0%) have completed study treatment. A one-sided, independent t-test demonstrated a significant reduction of at least 15% in COWS score from baseline to 60 minutes (t [24]=6.99; p<0.005), meaning that the mean percent reduction in COWS scores (52.2%) was clinically meaningful from baseline to 60 minutes after the start of active tAN therapy.

Across the entire cohort, COWS scores were reduced by 44.4% at 30 minutes and further reduced by 54.2% at 120 minutes. This reduction was further increased across Days 2 through 5 with a 63.4% reduction at Day 3 and a 74.6% reduction (to a COWS score of 3.7) at Day 5. The overall RMANOVA yielded significance, and Bonferroni pairwise comparisons yielded significant differences at each time point when compared to baseline (F[7,42]=9.90; p<0.005. At the conclusion of Day 1 (120 minutes), 95.2% of participants had a clinically significant reduction in the COWS score. In addition, 100% of participants passed an intranasal naloxone challenge by Day 5. Full study results will be presented.

Conclusion
Interim results from this study support use of the Sparrow tAN system for the reduction of opioid withdrawal symptoms.

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