Intranasal Oxytocin for the Treatment of Alcohol Use Disorder

Study Overview
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Brief Summary
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Primary: The primary objective of the study is to compare the efficacy of intranasal oxytocin in reducing the weekly percentage of heavy drinking days over the 10 weeks of maintenance treatment among subjects with moderate to severe Alcohol Use Disorder (AUD). A heavy drinking day is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for men. Secondary: Secondary objectives include assessment of other measures of the effects of oxytocin compared with placebo on reduction of alcohol use as well as effects on psychological assessments, alcohol craving, alcohol-related consequences, cigarette smoking and other nicotine use, retention in the study, safety, and application site (nares) tolerability throughout the study.

Official Title
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Randomized, Double Blind, Placebo-Controlled Trial of the Efficacy of Intranasal Oxytocin for the Treatment of Alcohol Use Disorder

Conditions
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Alcohol Use Disorder, Alcohol Misuse

Intervention / Treatment
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* Drug: Instranasal Oxytocin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be at least 21 years of age. Have a current (past 12 months) DSM-5 diagnosis of AUD (4 or more symptoms) assessed using the MINI neuropsychiatric interview version 7.0.2 (at least moderate severity, ICD-10-CM Code F10.20 alcohol dependence, uncomplicated). Have a BAC by breathalyzer equal to 0.000 when s/he signed the informed consent document (either just prior to or immediately after signing consent). Be seeking treatment for problems with alcohol reduction in drinking. Be able to verbalize an understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures, able to understand written and oral instructions in English and able to complete the questionnaires required by the protocol. Agree (if the subject is female and of child bearing potential) to use at least one of the following methods of birth control, unless she is surgically sterile, partner is surgically sterile or she is postmenopausal: oral contraceptives, contraceptive sponge, patch, double barrier (diaphragm/spermicidal or condom/spermicidal), intrauterine contraceptive system, etonogestrel implant, medroxyprogesterone acetate contraceptive injection, complete abstinence from sexual intercourse, and/or hormonal vaginal contraceptive ring. Be able to take intranasal investigational products and be willing to adhere to the investigational product regimen. Complete all assessments required at screening and baseline. Have a place to live in the 2 weeks prior to randomization and not be at risk that s/he will lose his/her housing by Study Week 14. Not anticipate any significant problems with transportation arrangements or available time to travel to the study site by Study Week 14. Not have any plans to move within Study Week 14 to a location which would make continued participation in the study impractical. Not have any unresolved legal problems that could jeopardize continuation or completion of the study. Provide contact information of someone, such as a family member, spouse, or significant other, who may be able to contact the subject in case of a missed clinic appointment. Be someone who in the opinion of the investigator would be expected to complete the study protocol. Agree to the schedule of visits, verbally acknowledge that s/he will be able to attend each scheduled visit, participate in phone visits and that s/he does not have any already scheduled events or a job that may substantially interfere with study participation. If taking a medication for depression or anxiety, must have been taking a stable dose in the 2-months prior to randomization and plan to continue during the study. This includes drugs such as the following: SSRIs Dual uptake inhibitors SNRIs Tricyclic antidepressants MAOIs Bupropion Not currently taking oxytocin and agree not to take non-study oxytocin for the duration of the study. Exclusion Criteria: Contact study site for exclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intranasal Oxytocin<br>Oxytocin, 35 IU per dose, intranasally twice-daily. One dose is defined as intranasal spray of 100 μL per each nostril x 5 sprays in alternating nostrils with a 30 second wait between sprays for a total dose volume of 500 μL. The total daily dose of oxytocin will be 70 IU/mL. | Drug: Instranasal Oxytocin<br>* Intranasal Oxytocin - concentrated formulation - 35 IU per dose<br>|
| Placebo Comparator: Instrasal Placebo<br>Identically matched placebo administered intranasally twice-daily. One dose is defined as intranasal spray of 100 μL per each nostril x 5 sprays in alternating nostrils with a 30 second wait between sprays for a total dose volume of 500 μL. | Drug: Instranasal Oxytocin<br>* Intranasal Oxytocin - concentrated formulation - 35 IU per dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Percentage of Heavy Drinking Days | The primary efficacy endpoint is the weekly percentage of heavy drinking days during the 10-week maintenance treatment period. A heavy drinking day is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for men. Drinking data will be collected by the Timeline Followback (TLFB) method. | 10 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with no heavy drinking days during treatment |  | 10 Weeks | 
| Percentage of subjects abstinent from alcohol during treatment |  | 10 weeks | 
| Percentage of subjects with at least a 1-level World Health Organization WHO) drinking risk category decrease |  | 10 weeks | 
| Percentage of subjects with at least a 2-level World Health Organization WHO) drinking risk category decrease |  | 10 weeks | 
| Percentage of days abstinent from alcohol per week |  | 10 weeks | 
| Weekly mean number of drinks per week |  | 12 weeks | 
| Weekly mean drinks per drinking day |  | 10 weeks | 
| MINI AUD Score at end of study |  | 12 weeks | 
| Cigarettes smoked per week among smokers |  | 10 weeks | 
| Abstinence from cigarette smoking among smokers |  | 12 weeks | 
| Other nicotine product use per week among other nicotine product users |  | 10 weeks | 
| Experiences in Close Relationships-Relationship Structures Questionnaire (ECR-RS) scores (attachment-related anxiety) |  | 12 weeks | 
| PROMIS sleep disturbances scores |  | 10 weeks | 
| PROMIS alcohol-related negative consequences scores |  | 10 weeks | 
| PROMIS pain interference scores |  | 10 weeks | 
| Profile of Moods States (POMS) scores (including subscale scores) |  | 10 weeks | 
| Urge to Drink Scores |  | 10 weeks |