Alcohol Use Disorder
Conditions
Keywords
Alcohol use disorder, Oxytocin, intranasal, Alcohol tolerance, Alcohol intake, Alcohol treatment, Alcohol, intravenous
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.
Detailed description
This pilot study is designed to demonstrate feasibility and provide preliminary data supporting use of intranasal oxytocin in treatment of alcohol use disorders. Specifically, experiments are planned to test the ability of oxytocin to reverse 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.
Interventions
DRUGIntranasal oxytocin
Initial dose 40 IU in 1 ml; 2 booster doses of 24 IU in 0.6 mls each, spaced about 1 hour apart
DRUGIntranasal placebo
Initial volume 1 ml; 2 booster volumes of 0.6 mls each, spaced about 1 hour apart
Sponsors
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, 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.
Intervention model description
2 Arms; both 2 session crossover design
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Effect of Alcohol - Craving | 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced. | 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. |
| Subjective Effects of Alcohol - Intoxication | 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced. | 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. |
| Stop Signal Response Task | 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced. | 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. |
| Stroop Test | 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced. | 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. |
| Alcohol Purchase Task (Variable OMax) | 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo | 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. |
Countries
United States
Participant flow
Recruitment details
Potential participants were contacted from our lab's recruiting database. Recruiting was active between January and May, 2022, and between October and November, 2023.
Pre-assignment details
Due to complications delaying the availability of the intranasal oxytocin and IV alcohol solutions needed for this project, we were unable to complete subjects in the self-administration arm of this study
Participants by arm
| Arm | Count |
|---|---|
| All Participants Demographic information is provided for all 6 participants combined. All 6 subjects participated in the clamp arm. The self-administration arm was not completed (see Overall Status). 3 participants had the Oxytocin session first, then Placebo; the other 3 had the reverse order (Placebo then Oxytocin). | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 35.5 Years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 6 | 4 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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.
Time frame: 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo
Population: All participants who completed both the Oxytocin and Placebo sessions are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Session (Clamp) | Alcohol Purchase Task (Variable OMax) | -1.0 dollars | Standard Error 2.1 |
| Placebo Session (Clamp) | Alcohol Purchase Task (Variable OMax) | -3.2 dollars | Standard Error 2.2 |
p-value: <0.5t-test, 2 sided
Primary
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.
Time frame: 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.
Population: All participants who completed both the Oxytocin and Placebo sessions are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Session (Clamp) | Stop Signal Response Task | -1.8 milliseconds | Standard Error 18 |
| Placebo Session (Clamp) | Stop Signal Response Task | -1.1 milliseconds | Standard Error 8 |
p-value: <1t-test, 2 sided
Primary
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.
Time frame: 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.
Population: All participants who completed both the Oxytocin and Placebo sessions are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Session (Clamp) | Stroop Test | -1.56 milliseconds | Standard Error 13.3 |
| Placebo Session (Clamp) | Stroop Test | -29.82 milliseconds | Standard Error 13.1 |
p-value: <0.04t-test, 2 sided
Primary
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.
Time frame: 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.
Population: All participants who completed both the oxytocin and placebo sessions were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Session (Clamp) | Subjective Effect of Alcohol - Craving | 1.6 units on a scale | Standard Error 11.4 |
| Placebo Session (Clamp) | Subjective Effect of Alcohol - Craving | 10.5 units on a scale | Standard Error 10.3 |
p-value: <0.6t-test, 2 sided
Primary
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.
Time frame: 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced.
Population: All participants who completed both the Oxytocin and Placebo sessions are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Session (Clamp) | Subjective Effects of Alcohol - Intoxication | 1.0 units on a scale | Standard Error 7.8 |
| Placebo Session (Clamp) | Subjective Effects of Alcohol - Intoxication | 7.8 units on a scale | Standard Error 13.2 |
p-value: <0.6t-test, 2 sided