Alcohol Use Disorders
Conditions
Keywords
Alcohol, Oxytocin, Stress reactivity
Brief summary
In comparison to the general population, military personnel and veterans are at increased risk of developing both substance use disorders (SUDs) and post-traumatic stress disorder (PTSD). Despite promising developments in the past decade, the treatment of patients with SUDs and comorbid PTSD is woefully inadequate (Back, 2010; Back et al., 2014; Brady et al., 2007; McCauley et al., 2012). One of the adverse effects of abused drugs is their long-term negative impact on social behavior that is thought to involve oxytocin (OT) dysregulation (McGregor et al., 2008). In preclinical and clinical experiments, local, intra-nasal, or systemic OT administration decreases activation of the amygdala in response to visual fearful/threatening stimuli (Kirsch et al., 2005), ameliorates the effects of stressful events, and decreases drug-taking and seeking behavior (McGregor et al., 2008; Baskerville and Douglas, 2010; Carson et al., 2010a; Bowen et al., 2011; Cox et al 2013). However, little attention has been focused on whether OT decreases SUD vulnerability after exposure to traumatic stress in preclinical or clinical studies. This clinical project will determine whether intra-nasally administered OT will decrease craving (Aim 1) to use alcohol and decrease stress reactivity (Aim 2) following exposure to laboratory-induced stress (Trier Social Stress Task) among veterans with a dual diagnosis of alcohol use disorder and PTSD.
Interventions
DRUGOxytocin
One 40 IU dose of intranasal oxytocin will be self-administered (5 puffs in each nostril) by participants.
DRUGPlacebo
Each participant will self-administer a 40 IU dose of intranasal saline.
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female; any race or ethnicity; age 21-65 years. * Female subjects will be required to complete the laboratory testing during the early to mid-follicular phase of their menstrual cycle (days 1-7 following the onset of menses). * Veteran of the US military; any service branch. * Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of the assessment instruments. * Subjects must be able to comprehend English. * Meet DSM-5 criteria for a current alcohol use disorder (assessed via the Mini International Neuropsychiatric Interview; MINI). Note that we will use the currently available diagnostic measure (MINI for DSM-IV) and will make appropriate modifications to update for compatibility with DSM-5. * Meet DSM-5 criteria for current PTSD (assessed via the Clinician Administered PTSD Scale; CAPS). Note that we will use the currently available assessment instrument (CAPS for DSM-IV), and will make appropriate modifications to update for compatibility with DSM-5. * A CAPS score of 50 or greater. * Subjects will be required to have at least 5 days of abstinence from alcohol or other substances (except caffeine or nicotine) prior to completing the laboratory testing, as verified by multiple methods including self-report, breathalyzer tests, and urine drug screen tests. * Subjects may also meet criteria for a mood disorder (except bipolar affective disorder, see
Exclusion criteria
) or anxiety disorders (e.g., agoraphobia, social phobia, generalized anxiety disorder). The inclusion of subjects with affective and anxiety disorders is essential because of the marked frequency of the co-existence of mood and other anxiety disorders among patients with PTSD and alcohol use disorders. * Subjects taking psychotropic medications will be required to be maintained on a stable dose for at least eight weeks before study initiation. This is because initiation or change of psychotropic medications during the course of the trial may interfere with interpretation of results. * Must consent to random assignment to oxytocin or placebo.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Craving | 2 hours | Using the Visual Analogue Scale (VAS), participants provided self-report ratings of subjective alcohol cravings on a scale of 1-10, with one being the lowest/better score, and 10 being the highest/worst outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stress Reactivity | 2 hours | Salivary Cortisol (μg/dL). Greater cortisol levels are indicative of greater stress reactivity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin Each participant will self-administer a 40 IU dose of intranasal oxytocin.
Oxytocin: One 40 IU dose of intranasal oxytocin will be self-administered (5 puffs in each nostril) by participants. | 35 |
| Control Each participant will self-administer a 40 IU dose of intranasal saline.
Placebo: Each participant will self-administer a 40 IU dose of intranasal saline. | 38 |
| Total | 73 |
Baseline characteristics
| Characteristic | Control | Total | Oxytocin |
|---|---|---|---|
| Age, Continuous | 47.82 years STANDARD_DEVIATION 11.27 | 48.36 years STANDARD_DEVIATION 10.51 | 48.94 years STANDARD_DEVIATION 9.75 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 44 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 26 Participants | 8 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 35 Participants | 67 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 38 |
| other Total, other adverse events | 0 / 35 | 0 / 38 |
| serious Total, serious adverse events | 0 / 35 | 0 / 38 |
Outcome results
Primary
Alcohol Craving
Using the Visual Analogue Scale (VAS), participants provided self-report ratings of subjective alcohol cravings on a scale of 1-10, with one being the lowest/better score, and 10 being the highest/worst outcome.
Time frame: 2 hours
Population: Main outcomes analyses were limited to male participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Alcohol Craving | 2.89 scores on a scale | Standard Deviation 2.63 |
| Control | Alcohol Craving | 3.08 scores on a scale | Standard Deviation 2.71 |
Secondary
Stress Reactivity
Salivary Cortisol (μg/dL). Greater cortisol levels are indicative of greater stress reactivity.
Time frame: 2 hours
Population: Main outcomes analyses were limited to male participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Stress Reactivity | .14 μg/dL | Standard Deviation 0.1 |
| Control | Stress Reactivity | .10 μg/dL | Standard Deviation 0.1 |