Intranasal Oxytocin for Methamphetamine Withdrawal in Women

Study Overview
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Brief Summary
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Methamphetamine use disorder (MUD) is a significant public health concern with burden to individuals, families and health systems estimated to cost over $5 billion annually in Australia. In 2016/17 there were 49,670 Australian treatment episodes for MUD, the first step of which typically involves inpatient withdrawal. Currently there are no approved medications to help manage methamphetamine withdrawal and consequently many people drop out of treatment prematurely, leaving them vulnerable to relapse. Oxytocin is a candidate medication that has the potential to increase treatment retention, reduce withdrawal syndrome severity, increase post-withdrawal treatment engagement and reduce relapse rates. The aim of this pilot study is to investigate whether intranasal oxytocin can improve withdrawal treatment outcomes in adult women with MUD. The study will examine usability and efficacy of intranasal oxytocin as a treatment for methamphetamine withdrawal in women. This will be explored by assessing length of stay in residential withdrawal, withdrawal symptom severity, post-discharge treatment engagement and relapse rates in a group of women who are prescribed intranasal oxytocin during their medically supervised methamphetamine withdrawal at a residential detoxification program. The safety of intranasal oxytocin will also be assessed. A secondary objective of the study is to conduct an exploratory analysis regarding participants' capacity to interact effectively with others, as well as changes in social networks and/or engagement with therapeutic services. There is an observational sub-study affiliated with this main pilot study that is optional for individuals recruited to the main pilot trial to additionally participate in. This sub-study aims to investigate how sleep quality and patterns change before, during, and after detoxification from methamphetamine in women. MUD and sleep disturbances have a complex bidirectional relationship. The use of methamphetamine is known to disrupt sleep quality and the circadian rhythm, although withdrawal from methamphetamine also induces significant sleep-wake cycle changes. There is evidence that methamphetamine disrupts functions regulated by the circadian rhythm. Furthermore, disruptions in circadian rhythms, including mutations in key genes, increases the propensity for addiction. Evaluation of how chronic methamphetamine use may disrupt rhythmicity, and vice versa, may provide invaluable information with regard to potential treatment options of methamphetamine use disorder. There has been little focus, so far, on the therapeutic potential of circadian rhythm modifiers as treatment options in the addiction space, as sleep disturbances have often been merely viewed as a consequence of substance use. Specific to the sub-study, participants will be asked to wear an actigraphy watch. The actigraphy watch device will be worn for at least 7 days prior to, 7 days during, and 7 days post methamphetamine detoxification. This is the only difference between the sub-study and the main pilot study; there are no other additional requirements or assessments involved in the actigraphy sub-study.

Official Title
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An Open Label Pilot Study of Intranasal Oxytocin for Methamphetamine Withdrawal in Women

Conditions
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Methamphetamine Use Disorder

Intervention / Treatment
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* Drug: Oxytocin nasal spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult females (aged ≥18 to ≤65 years), admitted to the Turning Point Addiction Medicine Unit. Meeting DSM-5 criteria for Methamphetamine Use Disorder, moderate or severe (assessed by treating physician on pre-admission to residential withdrawal). Able to comply with study protocols. Able to provide informed consent to participate. Exclusion Criteria: Non-English-speaking women. Women lactating, pregnant or of childbearing potential who are not willing to use an effective means of contraception for the duration of the trial. Meeting DSM-5 criteria for moderate-severe substance use disorder other than methamphetamine, nicotine and cannabis, as assessed by treating physician on pre-admission to residential withdrawal. Clinically significant or unmanaged medical or psychiatric illness (e.g., renal insufficiency, cirrhosis, unstable hypertension, unstable diabetes mellitus, seizure disorder, history of DSM-5 psychotic or bipolar disorder, current severe major depression, current suicidal ideation), assessed by treating physician on pre-admission to residential withdrawal. Current participation in another trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intranasal oxytocin<br>Participants will receive oxytocin by intranasal spray under clinician supervision (1 insufflation equating to an active dose of 24 IU) twice daily (i.e., 48 IU per day), delivered over 7 days of a residential inpatient withdrawal admission. | Drug: Oxytocin nasal spray<br>* Intranasal oxytocin, administered dose 24 international units (IU) twice daily, delivered over 7 days of a residential inpatient withdrawal admission.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay in the inpatient withdrawal unit | Medical chart review to determine number of days stayed in the inpatient withdrawal unit. | Admission Day 1 to Admission Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Methamphetamine withdrawal symptom severity | Individual average score across the participants' length of stay in the inpatient withdrawal unit on the Amphetamine Withdrawal Questionnaire (scores on this measure range from 0 to 40 with higher score indicating greater severity). | Admission Day 1 to Admission Day 7 | 
| Methamphetamine craving | Individual average score across the participants' length of stay in the inpatient withdrawal unit on the Visual Analogue Scale for Craving (scores on this measure range from 0 to 100, with higher scores indicating greater craving). | Admission Day 1 to Admission Day 7 | 
| Sleep dysfunction | Individual average score across the participants' length of stay in the inpatient withdrawal unit on the Insomnia Severity Index (scores on this measure range from 0 to 28, with higher scores indicating greater sleep dysfunction). | Admission Day 1 to Admission Day 7 | 
| Mood disturbance | Individual average score across the participants' length of stay in the inpatient withdrawal unit on the Abbreviated Profile of Mood States - Revised Version (total mood disturbance scores on this measure range from 0 to 116, with higher scores indicating greater disturbance) | Admission Day 1 to Admission Day 7 | 
| Methamphetamine relapse | Relapse is defined as a yes/no result for any methamphetamine use in the month following discharge from the withdrawal unit, as assessed using the Timeline Follow Back measure. | 1-month post-discharge | 
| Treatment engagement | Yes/No attendance at any form of treatment to assess treatment engagement at 1-month post-discharge. | 1-month post-discharge | 
| Therapeutic alliance | Working Alliance Inventory-Short Form Revised will be used to assess therapeutic alliance with nominated primary provider (scores on this measure range from 12 to 60, with higher scores indicating better therapeutic alliance). | 1-month post-discharge | 
| Incidence of adverse events | Number of participants with adverse events based on Systematic Assessment for Treatment Emergent Events. | Day 1 of admission to 1-month post-discharge | 
| Perceived burden of intranasal oxytocin | Individual average score across the participants' length of stay in the inpatient withdrawal unit on the Visual Analogue Scale for Medication Utilisation Burden (scores on this measure range from 0 to 100, with higher scores indicating greater perceived burden). | Admission Day 1 to Admission Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methamphetamine Use Disorder, Intranasal oxytocin, Actigraphy, Sleep