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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.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Martin H Plawecki, MD, PhD | Psychiatry, Indiana University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital | Indianapolis | Indiana | 46202 | United States |
The final raw dataset will be available to other researchers when we have collected all subjects, completed our own planned analyses, and, if warranted, sought and obtained funding based on the outcome of this pilot study.
The dataset will be available indefinitely
On request to the PI
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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
Potential participants were contacted from our lab's recruiting database. Recruiting was active between January and May, 2022, and between October and November, 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Oxytocin First, Then Placebo (Clamp) | Clamped alcohol exposure, repeated tests of subjective and cognitive effects of alcohol, 2 sessions (intranasal oxytocin or placebo), double blind 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 Intranasal placebo: Initial volume 1 ml; 2 booster volumes of 0.6 mls each, spaced about 1 hour apart |
| FG001 | Placebo First, Then Oxytocin (Clamp) | Clamped alcohol exposure, repeated tests of subjective and cognitive effects of alcohol, 2 sessions (intranasal oxytocin or placebo), double blind 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 Intranasal placebo: Initial volume 1 ml; 2 booster volumes of 0.6 mls each, spaced about 1 hour apart |
| FG002 | Oxytocin First, Then Placebo (Progressive Work) | Session in which participants could self-administer brief infusions of alcohol solutions. Opportunities for infusions could be earned by completing repetitions of a constant-attention button pressing task; the number of completions required increased over time (a progressive work schedule). Note no participants were enrolled in this Arm (see project termination for explanation). |
| FG003 | Placebo First, Then Oxytocin (Progressive Work) | Session in which participants could self-administer brief infusions of alcohol solutions. Opportunities for infusions could be earned by completing repetitions of a constant-attention button pressing task; the number of completions required increased over time (a progressive work schedule). Note no participants were enrolled in this Arm (see project termination for explanation). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All participants in this study
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All participants who completed both the oxytocin and placebo sessions were included. | Posted | Mean | Standard Error | units on a scale | 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced. |
|
Adverse event data were collected during 3 time periods: Oxytocin session day (~12 hours from arrival at to dismissal from Clinical Research Center) Between session day interval (21-28 days) Placebo session day (~12 hours from arrival at to dismissal from Clinical Research Center)
Adverse event data were collected during the sessions by tracking expected oxytocin side-effects at each testing block. Specific symptoms monitored included dizziness, dry mouth, runny nose, stomach pain, nausea, headache, or any other unusual feeling.
Adverse events were also collected unsystematically by asking the subject to report on their wellbeing and any unusual symptoms at study day intake, during the session, and during the post-session recovery period (3-6 hours).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Oxytocin Session | Measurements acquired during the Oxytocin Session | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ann E.K. Kosobud | Indiana University | 3172740087 | akosobud@iu.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 17, 2022 | Apr 9, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| D000428 | Alcohol Drinking |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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2 Arms; both 2 session crossover design
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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.
| Intranasal placebo | Drug | Initial volume 1 ml; 2 booster volumes of 0.6 mls each, spaced about 1 hour apart |
|
| 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 |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo Session (Clamp) | Measurements acquired during the placebo session |
|
|
|
| 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. | All participants who completed both the Oxytocin and Placebo sessions are included in the analysis. | Posted | Mean | Standard Error | units on a scale | 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced. |
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|
| 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. | All participants who completed both the Oxytocin and Placebo sessions are included in the analysis. | Posted | Mean | Standard Error | milliseconds | 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced. |
|
|
|
|
| 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. | All participants who completed both the Oxytocin and Placebo sessions are included in the analysis. | Posted | Mean | Standard Error | milliseconds | 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo, scheduled 3-4 weeks apart, order counter-balanced. |
|
|
|
|
| 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. | All participants who completed both the Oxytocin and Placebo sessions are included in the analysis. | Posted | Mean | Standard Error | dollars | 2 single day laboratory sessions, one with intranasal oxytocin, one with intranasal placebo |
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|
|
| 6 |
| 0 |
| 6 |
| 2 |
| 6 |
| EG001 | Placebo | Measurements acquired during the placebo session | 0 | 6 | 0 | 6 | 4 | 6 |
| EG002 | Between Session Interval | Events occurring between the first and second session day | 0 | 6 | 0 | 6 | 1 | 6 |
| Headache | General disorders | Systematic Assessment |
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| Infected Toe | Skin and subcutaneous tissue disorders | Systematic Assessment | Participant reported an active toe infection at session 2 that began sometime after session 1; was treated by physician. PI determined the infection was not related to study treatment. |
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| D004327 | Drinking Behavior |
| D001519 | Behavior |