Does Oxytocin Alter Tolerance to or Motivation for Alcohol

NCT05312008 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 10002
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study is intended to demonstrate feasibility and acquire preliminary data. If successful, this data could support a future project studying the effect of oxytocin on tolerance and alcohol seeking in humans.

Conditions

Alcohol Use Disorder

Keywords

Alcohol use disorder; Oxytocin, intranasal; Alcohol tolerance; Alcohol intake; Alcohol treatment; Alcohol, intravenous

Outcome Measures

Primary Outcomes (5)

• Subjective Effect of Alcohol - Craving

  Participants rated their subjective feeling of craving on a scale of 0-100. Tolerance to alcohol is assessed by subtracting subjective ratings at the beginning of the 2 hour alcohol infusion from ratings at the end; a negative value indicates tolerance. Possible scores ranged from -100 to 100; negative scores indicate the development of tolerance. Values reported here compare tolerance developed during the oxytocin session to tolerance developed during the placebo session.

  2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.

• Subjective Effects of Alcohol - Intoxication

  Participants rated their subjective feeling of intoxication on a scale of 0-100. Tolerance to alcohol is assessed by subtracting subjective ratings at the beginning of the 2 hour alcohol infusion from ratings at the end. Using this calculation, theoretical scores in this dataset could range from -100-100; negative scores indicate the development of tolerance. Values reported here compare tolerance developed during the oxytocin session to tolerance developed during the placebo session.

  2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.

• Stop Signal Response Task

  The Stop Signal task asks participants to respond as quickly as they can to one stimulus (the "Go" signal) but withhold this response when a second, much rarer stimulus appears (the "Stop" signal). Performance reported here uses the variable ssRT Med, which is an estimate of the time (in ms) needed to stop and withdraw the response; alcohol is known to increase ssRT Med. To assess tolerance, the value of ssRT Med measured at the beginning of the 2 hour alcohol clamp was subtracted from the value measured at the end. The theoretical range of possible scores on this measure range from about -100 to 200; negative scores indicate the development of tolerance. Values reported here compare tolerance developed during the oxytocin session to tolerance developed during the placebo session.

  2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.

• Stroop Test

  The Stroop Interference task asks participants to respond to one aspect of a stimulus (in this case, the color of the text in which a word is printed) under conditions in which the word meaning either enhances or interferes with the task (for example, the word Green in a Green font speeds performance, while the word Green in a Yellow font slows performance). Tolerance to alcohol was assessed by subtracting response latency (ms) on correct trials at the beginning of the 2 hour alcohol infusion from latency on correct trials at the end. Theoretical scores ranged from about -200 to 250; negative scores indicate the development of tolerance. Values reported here compare tolerance developed during the oxytocin session to tolerance developed during the placebo session.

  2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.

• Alcohol Purchase Task (Variable OMax)

  The Alcohol Purchase task (APT) tests the value participants place on alcohol at specific times and conditions of the experimental session. To complete the APT, participants fill out a table reporting how many drinks (allowed range 0-50) they would purchase during an evening out, for a cost ranging from $0 to $30/drink. From this, a value for # of drinks \* cost of drink is calculated; OMax is the highest amount in dollars that a participant would spend (possible range = $0 to $1,500). Tolerance to the effect of alcohol is calculated as OMax (end of infusion) - OMax (beginning of infusion), possible values range from -$1,500 to $1,500. Negative scores indicate the development of tolerance. Values reported here compare tolerance developed during the oxytocin session to tolerance developed during the placebo session.

  2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo

Study Arms (2)

Clamp

EXPERIMENTAL

Repeated subjective and cognitive tests during a 4 hour session that includes a baseline period, an oxytocin or placebo delivery, absorption and testing period, and a 2 hour alcohol clamp. Oxytocin or placebo were delivered intranasally in two sessions, scheduled 3-4 weeks apart, double blind.

Drug: Intranasal oxytocin; Drug: Intranasal placebo

Progressive work for alcohol

EXPERIMENTAL

Progressive work alcohol exposure, 2 sessions (intranasal oxytocin or placebo), double blind. Note this Arm was not completed (see Overall Status for explanation of study termination)

Drug: Intranasal oxytocin; Drug: Intranasal placebo

Interventions

Intranasal oxytocin DRUG

Initial dose 40 IU in 1 ml; 2 booster doses of 24 IU in 0.6 mls each, spaced about 1 hour apart

Clamp; Progressive work for alcohol

Intranasal placebo DRUG

Initial volume 1 ml; 2 booster volumes of 0.6 mls each, spaced about 1 hour apart

Clamp; Progressive work for alcohol

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Heavy alcohol drinkers.
• Able to understand/complete questionnaires and procedures in English.
• Have venous access sufficient to allow blood sampling.

You may not qualify if:

• Latex allergy.
• Nasal condition that compromises delivery and/or absorption of intra-nasal oxytocin
• Pregnant or breast-feeding women.
• Desire to be treated for any substance use disorder or court ordered to not drink alcohol
• Medical disorders or other conditions such as alcohol withdrawal seizures or delirium tremens that may influence study outcome or participant safety.
• Positive urine drug screen for amphetamines/ methamphetamines, barbiturates, benzodiazepines, cocaine, opiates, or phencyclidine if determined by the PI to adversely affect participant safety or data integrity.
• Medications (past 30 days) that could influence participant safety or data integrity (e.g. antidepressants, antipsychotics, benzodiazepines, etc.) as determined by the PI.
• DSM 5 Disorders (other than alcohol) or current/history of neurological disease of cerebral origin, or head injury with \> 20 min loss of consciousness, if determined by the PI to affect participant safety or data integrity.
• Positive breath alcohol reading at beginning of the experimental session.
• Actively suicidal (for example, any current suicidal intent, including a plan) or are at serious suicidal risk, by clinical judgment of the PI.
• Any condition for which the PI and investigative team determine it is unsafe or not prudent to enroll a participant.

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

University Hospital

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Alcoholism; Alcohol Drinking

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Drinking Behavior; Behavior

Results Point of Contact

• Title: Dr. Ann E.K. Kosobud
• Organization: Indiana University

akosobud@iu.edu

3172740087

Study Officials

• Martin H Plawecki, MD, PhD

  Psychiatry, Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The pharmacy will prepare the intranasal spray (both oxytocin and placebo) and deliver it in coded syringes to the lab. Investigators, laboratory staff and subjects will be unaware of the identity of the spray on session days. The pharmacy will provide the unmasking information after all sessions are completed.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Model Details: 2 Arms; both 2 session crossover design

Study Record Dates

• First Submitted: February 26, 2022
• First Posted: April 5, 2022
• Study Start: January 16, 2022
• Primary Completion: December 21, 2023
• Study Completion: December 21, 2023
• Last Updated: March 4, 2025
• Results First Posted: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: The dataset will be available indefinitely
• Access Criteria: On request to the PI

Locations

US (1)