Laboratory Studies on Oxytocin for Treatment of Alcohol Use Disorder

Phase 1

Completed

• Conditions: Alcoholism; Alcohol Related Disorders
• Interventions: Drug: placebo; Drug: oxytocin

• Registration Number: NCT02407340
• Lead Sponsor: Johns Hopkins University

Brief Summary

This study will examine the utility of the neuropeptide oxytocin (OT) as a potential new medication for the treatment of Alcohol use disorder (AUD). Non-treatment seeking men and women with AUD will be enrolled in a double blind placebo controlled phase I clinical trial. Participants will complete an 7-day inpatient protocol. During the first 3 days of the inpatient protocol, participants will complete alcohol abstinence in which withdrawal symptoms are measured,and urine will be collected to determine withdrawal symptom severity and urine levels of the stress hormone cortisol. Participants will then complete 3 laboratory procedures which measure 1) stress response, 2) motivation to drink alcohol and 3) subjective and physiological effects of alcohol. Finally, because participants are individuals with AUD, investigators will administer a brief intervention to address their risky alcohol drinking and problems before discharge.

Detailed Description

This study will lay the necessary groundwork for future comprehensive research to examine the utility of the neuropeptide oxytocin (OT) as a potential new medication for the treatment of Alcohol use disorder (AUD). OT modulates a number of key systems involved in addiction processes, including dopamine (DA) mesolimbic reward circuitry, and hypothalamic-pituitary-adrenal (HPA) axis and corticotrophin-releasing factor (CRF) stress systems, and has low abuse liability. Our overarching hypothesis is that OT will attenuate several measures thought to drive compulsive alcohol drinking and relapse. Specifically, investigators will examine whether OT decreases acute stress responses, alleviates alcohol withdrawal symptoms, reduces craving and motivation to drink, and decreases alcohol self-administration. Since interactions with alcohol are an important focus of our study, investigators will enroll non-treatment seeking heavy drinkers with AUD in a double blind, placebo controlled inpatient protocol. Subjects will be randomized to receive intranasal OT (40 IU/dose) or placebo 3 times daily. Participants will complete alcohol detoxification; investigators will measure alcohol withdrawal symptoms, craving, and 24-hr urinary free CORT. Participants will then complete 3 laboratory procedures in fixed order. The Trier Social Stress Test (TSST) which includes public speaking and performance of mental arithmetic will be used to examine subjective and physiological stress responses. An alcohol motivated responding (AMR) procedure will be used to examine subjects' responding to earn either drinks or money. A cumulative alcohol-dosing (CAD) procedure will be used to examine physiological and subjective responses across several blood alcohol levels. cortisol (CORT) levels will also be assessed. This study will provide new information on OT efficacy across a range of different measures predictive of alcohol use and misuse, and, if OT shows efficacy, help clarify the mechanism of OT action.

Study Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-03-30
• Study First Submitted QC: 2015-04-01
• Study First Posted: 2015-04-02
• Primary Completion: 2017-06-15
• Study Completion: 2017-06-15
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-30
• Last Update Posted: 2017-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

• Healthy 21-50 years old male and female subjects
• Must meet Diagnostic and Statistical Manual (DSM) -V criteria for AUD and not be seeking treatment
• Actively drinking
• Positive blood phosphatidylethanol (PEth) blood test

Exclusion Criteria

• Current DSM-V major current mood or anxiety disorder or drug use disorder (excluding alcohol and nicotine use disorders, and moderate-severe cannabis use disorder); in or in need of treatment
• Drug use in last 30 days and/or positive urine toxicology screens (excluding marijuana)
• History of seizure disorder or closed head trauma
• History of withdrawal-related seizures or serious alcohol withdrawal symptoms
• HIV positive
• Neuroendocrine disorder
• Any serious medical condition that would place subject at risk or interfere with study participation
• Liver function tests more than 3 times normal at screening
• Prescription medications in last 3 months that could affect central nervous system or HPA axis function
• Women who are pregnant, nursing or planning pregnancy cannot participate

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Intranasal placebo administered 3 times daily for 1 week
Oxytocin	oxytocin	intranasal oxytocin - 40 International Units (IU) dose administered 3 times daily for 1 week

Primary Outcome Measures

Name	Time	Method
Alcohol drinking	1 day	Group mean number of Standard Drink Units earned and self-administered in the laboratory session

Secondary Outcome Measures

Name	Time	Method
alcohol effects	1 day	Group mean stimulation and sedation subscale scores on the biphasic alcohol effects scale (BAES), a 14-item scale consisting of adjectives that describe the stimulant- and sedative-like effects of alcohol. The items are presented in alphabetical order, and are rated on an 11-point rating scale from 0=Not at All to 10=Extremely after controlled alcohol administration.
side effects	1 week	side effects reported on the Systematic Assessment for Treatment Emergent Events (SAFTEE)
Salivary cortisol	1 day	Peak and Area under the curve salivary cortisol levels after trier social stress test

Trial Locations

Locations (1)

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States