The Effects of Oxytocin on Startle Hyperreactivity in Patients With AUD and PTSD

Study Overview
=================
Brief Summary
-----------------
This study will investigate the effects of oxytocin on alcohol-related behaviors, social abilities, and physiological startle responses in healthy individuals and patients with posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) using a randomized, placebo-controlled, dose-tiered, between-subject study design. Specifically, the investigators will determine if intranasal administration of a single dose of the pro-social neuropeptide oxytocin decreases alcohol-related approach bias and cravings, enhances social abilities, and decreases physiological hyperactivity. The investigators will also determine the optimal dose to achieve these effects and will explore psychosocial predictors of responses to oxytocin. The proposed work has the potential to yield a novel pharmacological treatment for AUD and PTSD, both leading causes of disability in the US Military for which currently available treatments are inadequate.

Official Title
-----------------
The Effects of Oxytocin on Social Ability, Alcohol Approach Bias, and Startle Hyperreactivity in Veterans With Alcohol Use Disorder and Post Traumatic Stress Disorder

Conditions
-----------------
Stress Disorders, Post-Traumatic, Alcoholism

Intervention / Treatment
-----------------
* Drug: Oxytocin
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ages 18 to 75 (inclusive) Current DSM-V diagnosis of PTSD Current (past month) DSM-V diagnosis of a moderate to severe Alcohol Use Disorder Exclusion Criteria: Current or lifetime psychotic disorders, such as schizophrenia or bipolar disorder Dementia or other neuropsychiatric disorders involving cognitive deficits or active symptoms impairing their ability to complete study tasks. Subjects known to have clinically significant unstable medical conditions, including but not limited to clinically significant renal disease. Use of disulfiram, naltrexone, or acamprosate for alcohol use disorder in the past week. Needing acute medical detoxification from alcohol based on a score of 12 or more on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-AD); Subjects who are legally mandated to participate in an alcohol treatment program. Subjects who have had a suicide attempt in the past 6 months or suicidal ideation in the 90 days prior to enrollment. Subjects with seizure disorders that require anticonvulsant medications Positive urine pregnancy test, women meeting DSM-V criteria for premenstrual dysphoric disorder or with diseases likely to influence hormonal or neuroendocrine status Sensitivity to preservatives (in particular E 216, E 218 and chlorobutanol hemihydrate) Nasal obstruction, discharge, or bleeding Taking testosterone or estrogen/progesterone supplement, or 5HT1a agonists/antagonists, as these agents can alter oxytocin levels

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Subjects will receive either 20IU or 40IU intranasal oxytocin | Drug: Oxytocin<br> <br> * Other names: Syntocinon;|
| Placebo Comparator: Placebo<br>Subjects will receive intranasal saline spray | Other: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Social Perception measured by score on the Reading the Eyes in the Mind Test |  | Participants will complete the task 60 minutes following test drug administration. This will occur 3 times during the study period, with each visit separated by at least 7 days. The total study duration will be an average of 4 weeks per subject. | 
| Alcohol Approach Bias measured by score on the Approach Avoidance Task |  | Participants will complete the task 65 minutes following test drug administration. This will occur 3 times during the study period, with each visit separated by at least 7 days. The total study duration will be an average of 4 weeks per subject. | 
| Startle Hyperactivity measured by heart rate change score in response to startle stimuli |  | Participants will complete the task 70 minutes following test drug administration. This will occur 3 times during the study period, with each visit separated by at least 7 days. The total study duration will be an average of 4 weeks per subject. | 
| Craving will measured by heart rate change score in response to a Cue-Induced Craving task |  | Participants will complete the task 80 minutes following test drug administration. This will occur 3 times during the study period, with each visit separated by at least 7 days. The total study duration will be an average of 4 weeks per subject. | 
| Craving will measured by skin conductance change score in response to a Cue-Induced Craving task |  | Participants will complete the task 80 minutes following test drug administration. This will occur 3 times during the study period, with each visit separated by at least 7 days. The total study duration will be an average of 4 weeks per subject. | 
| Theory of Mind will me measured by score on the Theory of Mind Geometric Task |  | Participants will complete the task 90 minutes following test drug administration. This will occur 3 times during the study period, with each visit separated by at least 7 days. The total study duration will be an average of 4 weeks per subject. | 
| Social Threat Processing will be measured by score on the Social Dot Probe Task |  | Participants will complete the task 100 minutes following test drug administration. This will occur 3 times during the study period, with each visit separated by at least 7 days. The total study duration will be an average of 4 weeks per subject. | 
| Social Cognition will be measured by score on the Facemorph Task. |  | Participants will complete the task 105 minutes following test drug administration. This will occur 3 times during the study period, with each visit separated by at least 7 days. The total study duration will be an average of 4 weeks per subject. | 
| Working Memory will be measured by score on the Symmetry Span Task |  | Participants will complete the task 120 minutes following test drug administration. This will occur 3 times during the study period, with each visit separated by at least 7 days. The total study duration will be an average of 4 weeks per subject. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
oxytocin, PTSD, Alcohol Use Disorder, social cognition, craving, fear-potentiated startle