Does Oxytocin Alter Tolerance to or Motivation for Alcohol

Sponsor

Indiana University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05312008

Collaborator

(none)

Enrollment

Location

Arms

11.5

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This pilot study will seek evidence that oxytocin, compared to placebo, reverses tolerance and alcohol seeking in humans.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Intranasal oxytocin Drug: Intranasal placebo	Phase 2

Detailed Description

This pilot study will seek evidence that intranasal oxytocin reverses tolerance and alcohol seeking in humans by employing state-of-the-art computer-assisted intravenous alcohol administration. Two separate experiments will be run. In the first, tolerance will be assessed using sensitive tests of subjective response and cognitive function during an intravenous infusion that maintains a steady breath and therefore brain exposure to alcohol. In the second, an intravenous alcohol self-administration paradigm that requires increasing effort for each additional infusion will be used to assess change in motivation for alcohol. Demonstrating that oxytocin (compared to placebo) worsens test performances in alcohol-dependent individuals and/or reduces the compulsive drive to self-administer alcohol would be strong evidence for its potential to treat alcohol use disorders.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

2 Arms; both 2 session parallel design2 Arms; both 2 session parallel design

Masking:

Double (Participant, Investigator)

Masking Description:

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..

Primary Purpose:

Basic Science

Official Title:

Does Oxytocin Alter Tolerance to Alcohol or Motivation for Alcohol in Heavy Drinking Human Subjects: Testing a Novel Anti-Addiction Mechanism

Actual Study Start Date :

Jan 16, 2022

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clamp Clamped alcohol exposure, repeated tests of subjective and cognitive effects of alcohol, 2 sessions (intranasal oxytocin or placebo), double blind	Drug: Intranasal oxytocin Initial dose 40 IU in 1 ml; 2 booster doses of 24 IU in 0.6 mls each, spaced about 1 hour apart Drug: Intranasal placebo Initial volume 1 ml; 2 booster volumes of 0.6 mls each, spaced about 1 hour apart
Experimental: Progressive work for alcohol Progressive work alcohol exposure, 2 sessions (intranasal oxytocin or placebo), double blind	Drug: Intranasal oxytocin Initial dose 40 IU in 1 ml; 2 booster doses of 24 IU in 0.6 mls each, spaced about 1 hour apart Drug: Intranasal placebo Initial volume 1 ml; 2 booster volumes of 0.6 mls each, spaced about 1 hour apart

Arm

Intervention/Treatment

Experimental: Clamp

Clamped alcohol exposure, repeated tests of subjective and cognitive effects of alcohol, 2 sessions (intranasal oxytocin or placebo), double blind

Drug: Intranasal oxytocin

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

Drug: Intranasal placebo

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

Experimental: Progressive work for alcohol

Progressive work alcohol exposure, 2 sessions (intranasal oxytocin or placebo), double blind

Drug: Intranasal oxytocin

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

Drug: Intranasal placebo

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

Outcome Measures

Primary Outcome Measures

Subjective effects of alcohol [2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo]
Difference between oxytocin compared to placebo sessions in tolerance to the subjective effects of alcohol as measured using a self-report questionnaire
Stop Signal Response task [2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo]
Difference between oxytocin compared to placebo sessions in tolerance to the effects of alcohol on stop signal response times and performance
Stroop test [2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo]
Difference between oxytocin compared to placebo sessions in tolerance to the effects of alcohol on stroop test response times and performance
Alcohol self-administration [2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo]
Difference between oxytocin versus placebo sessions in motivation for alcohol as indicated by number of alcohol infusions earned, progressive ratio breakpoint, and/or breath alcohol concentration achieved.
Alcohol purchase task [2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo]
Difference between oxytocin versus placebo sessions in motivation for alcohol as indicated by the maximum price subjects endorse.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

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.