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Individuals with alcohol use disorder (AUD) will complete one functional Magnetic Resonance Imaging (fMRI) scanning visit. Prior to the scan, individuals will receive a nasal spray of either 24 international units (IU) of oxytocin (OT), or placebo (PBO). During the scan, they will perform the Montreal Imaging Stress Task (MIST), a social stress task. Subjective craving and anxiety data will be collected.
Participants: Twenty-four individuals with AUD will be recruited through the Clinical Intake and Assessment (CIA) Core of the Alcohol Research Center (ARC). Screening and basic assessments will be conducted by the CIA Core to determine eligibility and suitability for participation in this pilot project. Each individual will sign an Institutional Review Board (IRB)-approved informed consent form.
Study Visit Assessments: The Drinking Motives Questionnaire Revised will be used to assess motivation for drinking across four subscales: (1) coping motives; (2) social motives; (3) conformity motives; and (4) enhancement motives. The Form 90 will be used to assess daily alcohol consumption in the 90 days prior to the study visit and the time from last drink . A modification of the Within Session Rating Scale will be used to assess craving and mood.
Study Visit Procedures: Participants will be asked to arrive at the Addiction Sciences Division on the study visit day. Female participants will have their urine tested for pregnancy. Females who test positive for pregnancy will be excluded. All participants will be tested for drugs of abuse and alcohol. Patients testing positive for drugs, with the exception of marijuana, will be excluded; patients testing positive for alcohol may be re-scheduled. Participants will be asked about substance use in the last 90 days and will fill out the Drinking Motives Questionnaire. Subjects who have not had a research physical exam within the last 30 days will have a physical completed. They will then be escorted to the scanner at 30 Bee Street.
The study will use a double-blind placebo controlled design. Intranasal OT (n=12) or PBO (n=12) sprays will be administered at 11:30 am, approximately 45 min prior to the scanning session. This dose and timing of OT administration were selected based on the literature.
MIST Procedure: The study will use a block design of three, 6-min runs separated by 2-min of rest for feedback, for a total of 24 min. During each run, participants will be exposed to 40-sec blocks of three different conditions (rest, control, and experimental). Prior to the task, participants will are shown images of what the screen will look like during each condition. The participants will be instructed to relax during the rest condition and focus on the screen. During the control condition, the participants will be asked to answer math problems as accurately as possible but will also be told that their responses will not be recorded. During the experimental condition, the participants will be asked to perform the math task as quickly and accurately as possible. A performance bar located on the screen will allow them to see their performance as compared to an "average" person. The participants will be told that the average person would answer about 85% of the problems correctly; however, the program limits the participants' performance rate to between 35-45%. A time limit will be enforced throughout the experimental condition. After each run, the participants will be given negative feedback from the investigator.
Blood Oxygen Level Dependent (BOLD)-fMRI Procedure: Data will be acquired on a Siemens Trio 3T scanner in MUSC's Center for Biomedical Imaging. For co-registration and normalization of functional images, a high resolution T1-weighted Magnetization-Prepared Rapid Acquisition with Gradient Echo (MPRAGE) anatomical image will be acquired with the following parameters: Time of Repetition (TR)= 2100 ms, Echo Time (TE)= 4.18 ms, flip angle= 12°, field of view= 256 mm, slice thickness= 1.0 mm. The scanning planes will be oriented parallel to the anterior commissure-posterior commissure line. Participants will be asked to relax and keep their eyes opened and fixed on a cross-hair for 6 min while resting state data are collected. Participants will then complete the MIST. T2*-weighted gradient-echo planar images (EPI) will be acquired with the following parameters: TR= 2000 ms, TE= 27 ms, flip angle= 76º, matrix 64 x 64, field of view= 23 cm, slice thickness= 3.7 mm with no gap, with 36 slices to cover the entire brain.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oxytocin/alcohol use disorder | Experimental | Participants will receive 24 IU of oxytocin prior to completing fMRI scanning procedures. |
|
| Placebo/Alcohol use disorder | Placebo Comparator | Participants will receive placebo (saline solution) prior to completing fMRI scanning procedures. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxytocin | Drug | The neuropeptide oxytocin (OT) increases social approach, trust, and reduces anxiety to social stress. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Corticolimbic Functional Connectivity Based on fMRI Blood Oxygenation Level Dependent (BOLD) Response During the Stress Versus Neutral Conditions of the Montreal Imaging Stress Test Task Averaged Over the Second and Third Functional Runs | Corticolimbic functional connectivity will be determined using psychophysiological interaction (PPI) modeling. The left and right amygdala will serve as seed regions. Connectivity of each seed region with the homologous orbitofrontal cortex region will be represented as a parameter estimate, yielding one parameter estimate for right amygdala-right orbitofrontal connectivity and one parameter estimate for left amygdala-left orbitofrontal connectivity per subject. | 60 minutes following medication (oxytocin or placebo) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jane Joseph, PhD | Medical University of South Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Addiction Sciences Division-Medical University of South Carolina | Charleston | South Carolina | 29403 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Oxytocin/Alcohol Use Disorder | Participants will receive 24 IU of oxytocin prior to completing fMRI scanning procedures. Oxytocin: The neuropeptide oxytocin (OT) increases social approach, trust, and reduces anxiety to social stress. |
| FG001 | Placebo/Alcohol Use Disorder | Participants will receive placebo (saline solution) prior to completing fMRI scanning procedures. Placebo: Saline solution. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Oxytocin/Alcohol Use Disorder | Participants will receive 24 IU of oxytocin prior to completing fMRI scanning procedures. Oxytocin: The neuropeptide oxytocin (OT) increases social approach, trust, and reduces anxiety to social stress. |
| BG001 | Placebo/Alcohol Use Disorder |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Corticolimbic Functional Connectivity Based on fMRI Blood Oxygenation Level Dependent (BOLD) Response During the Stress Versus Neutral Conditions of the Montreal Imaging Stress Test Task Averaged Over the Second and Third Functional Runs | Corticolimbic functional connectivity will be determined using psychophysiological interaction (PPI) modeling. The left and right amygdala will serve as seed regions. Connectivity of each seed region with the homologous orbitofrontal cortex region will be represented as a parameter estimate, yielding one parameter estimate for right amygdala-right orbitofrontal connectivity and one parameter estimate for left amygdala-left orbitofrontal connectivity per subject. | Posted | Mean | Standard Deviation | contrast of parameter estimates | 60 minutes following medication (oxytocin or placebo) |
|
6 months
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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/Alcohol Use Disorder | Participants will receive 24 IU of oxytocin prior to completing fMRI scanning procedures. Oxytocin: The neuropeptide oxytocin (OT) increases social approach, trust, and reduces anxiety to social stress. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Laura Lohnes | Medical University of South Carolina | 843-792-7709 | lohnes@musc.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 | Jan 4, 2018 | Sep 20, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D010121 | Oxytocin |
| ID | Term |
|---|---|
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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| Placebo | Drug | Saline solution. |
|
Participants will receive placebo (saline solution) prior to completing fMRI scanning procedures. Placebo: Saline solution. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo/Alcohol Use Disorder | Participants will receive placebo (saline solution) prior to completing fMRI scanning procedures. Placebo: Saline solution. |
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 0 |
| 5 |
| EG001 | Placebo/Alcohol Use Disorder | Participants will receive placebo (saline solution) prior to completing fMRI scanning procedures. Placebo: Saline solution. | 0 | 5 | 0 | 5 | 0 | 5 |
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| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |