Protocol for an open label pilot study of intranasal oxytocin for methamphetamine withdrawal in women (mOXY trial)

Abstract

Background Methamphetamine Use Disorder (MAUD) is associated with major public heath burden worldwide, yet medication treatment options are lacking. For many patients, the first step in a treatment episode is admission to a residential detoxification or rehabilitation unit for withdrawal, however unplanned early discharge is common, and evidence suggests treatment benefits may be short-lived. Pharmacotherapy candidates for methamphetamine withdrawal have thus far failed to show sufficient benefit; there are currently no FDA/TGA approved medications for treatment of MAUD. Oxytocin is a candidate medication with potential to increase treatment retention and reduce withdrawal symptom severity and relapse rate. It has shown promise in the context of cocaine, cannabis and alcohol use disorders. Central neuro-modulatory effects of oxytocin may aide in alleviating withdrawal symptoms and craving, evident in preclinical and clinical studies. Further research is necessary, as is addressing the critical importance of sex differences in addiction treatment. Therefore, we aim to investigate the feasibility of intranasal oxytocin as a treatment for methamphetamine withdrawal, whilst targeting the significant gap in research by focusing on women. Methods This open label pilot trial will investigate the feasibility of intranasal oxytocin as a treatment for methamphetamine withdrawal in women. Oxytocin is administered twice daily to 10 women during a 7-day residential inpatient withdrawal admission. The primary objective is to assess feasibility as measured through the proportion of screen failures to those who received the study drug. Secondary objectives are assessment of length of stay up to 7 days in the inpatient unit. withdrawal symptom severity, relapse rates and treatment engagement at 1-month post discharge, and safety and tolerability of intranasal oxytocin. Changes in social functioning and social cognition from baseline to 1-month post-discharge will also be assessed as exploratory endpoints. Discussion Outcomes from this proof-of-concept study will inform the feasibility and endpoints of a full-scale randomised clinical trial, as well as provide preliminary data on the possible mechanisms underlying the therapeutic effects of oxytocin. Furthermore, the study will build critically needed research capacity in female-specific MAUD medication treatment. Trial Registration ClinicalTrials.gov Identifier: NCT05709353, registered February 14^th 2023 (Protocol version 2.0, 6^th January 2023; https://www.clinicaltrials.gov/study/NCT05760807).