Oxytocin Suppresses Substance Use Disorders Associated With Chronic Stress

The purpose of this study is to determine whether oxytocin will decrease craving to use drugs/alcohol and stress reactivity following exposure to laboratory-induced stress among Active Duty Service Members with a dual diagnosis of alcohol/substance use disorder (ASUD) and post-traumatic anxiety.

Study Overview

• Status: Completed
• Conditions: Anxiety Disorders; Stress Disorders, Post-Traumatic; Substance Use Disorders; Alcohol Use Disorder
• Intervention / Treatment: Drug: Oxytocin; Drug: Placebo

Detailed Description

The purpose of this study is to determine whether intra-nasally administered oxytocin will decrease craving to use alcohol and stress reactivity following exposure to laboratory-induced stress among Active Duty Service Members (AD SMs) with a dual diagnosis of alcohol/substance use disorder (ASUD) and post-traumatic anxiety (i.e., PTSD or anxiety disorder NOS).

This is a 2-arm placebo controlled study. Subjects will complete a battery of self-report questionnaires and behavioral interviews. Baseline assessments of subjective (craving, stress), physiologic (HR, BP), and neuroendocrine measures (salivary cortisol) will be collected. These same assessments will be repeatedly collected throughout the testing portion of the study. Subjects will receive acute administration of intra-nasal oxytocin or placebo and will then be exposed to a laboratory-induced social stressor. They will be asked to give a short speech and perform arithmetic in front of a panel of judges. Following the task, additional post-task assessments of the subjective, physiological, and neuroendocrine measures will be completed over the next hour.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92106
      • Naval Medical Center San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Active Duty Service Members, any service branch; age 18-65 years.
• Meets clinician assessment for current PTSD OR anxiety disorder NOS OR scores on DASS > 10 on Anxiety or > 19 on Stress.
• Meets clinician assessment for alcohol use disorder (AUD) OR scores >8 on AUDIT.
• If meet current or lifetime criteria for another substance disorder, must indicate that AUD is primary.
• Subjects taking psychotropic medications will be required to be maintained on a stable dose for at least two weeks before study initiation (unless at physician's discretion following psychological consult).
• Negative urine drug screen test and BAC =0.
• Able to comprehend English.
• Able to provide informed consent and function at an intellectual level sufficient to allow completion of the assessment instruments.
• Must consent to random assignment to oxytocin or placebo.

Exclusion Criteria:

• Positive urine drug screen (except marijuana) or BAC > 0.
• Untreated subjects currently symptomatic of psychotic or bipolar affective disorders.
• Subjects with current suicidal or homicidal ideation and intent, who would present a serious suicide risk.
• Subjects on psychotropic drugs that have been initiated during the past 2 weeks (unless approved at physician's discretion following psychological consult).
• Subjects with a history of a major medical illness (e.g., endocrine, cardiovascular, central nervous system disorders, peripheral neuropathy, or pulmonary disease) or other acute or unstable medical condition that might interfere with safe conduct of the study or accurate interpretation of the results.
• Subjects experiencing withdrawal symptoms as reported by Clinician or systolic BP≥160 mmHg, diastolic BP ≥100 mmHg and resting HR ≥100 bpm.
• Subject is considered unsuitable for the study in the opinion of study PI or AIs for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxytocin; Intra-nasal oxytocin (40 IUs; 5 puffs in each nostril)	Drug: Oxytocin; Intranasal oxytocin 40 IU; Other Names: Syntocinon nasal spray
Placebo Comparator: Placebo; Intra-nasal saline placebo (5 puffs in each nostril)	Drug: Placebo; Intranasal saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Craving to Use Alcohol Rating (Visual Analog Scale)	The Visual Analog Scale (VAS) is a horizontal line of fixed 100 mm length. The ends are defined as the extreme limits of the parameter from the left (least) to the right (most). Subjects mark the point on the line that represents their perception of the parameter. The score is determined by measuring in millimeters from the left end of the line to the point that the patient marks. The score range is 0-100, with higher scores indicating higher cravings.	Change from baseline to post-drug at 20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Stress Rating (Visual Analog Scale)	The Visual Analog Scale (VAS) is a horizontal line of fixed 100 mm length. The ends are defined as the extreme limits of the parameter from the left (least) to the right (most). Subjects mark the point on the line that represents their perception of the parameter. The score is determined by measuring in millimeters from the left end of the line to the point that the patient marks. The score range is 0-100, with higher scores indicating higher stress.	Change from baseline to post-drug at 20 minutes

Collaborators and Investigators

• Sponsor: Jennifer Mitchell
• Collaborators: United States Department of Defense; United States Naval Medical Center, San Diego; Congressionally Directed Medical Research Programs; Eisenhower Army Medical Center
• Investigators: Principal Investigator: Mardi Smith, PhD, United States Naval Medical Center, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2017
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: April 14, 2016
• First Posted (Estimate): April 19, 2016

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: September 21, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Alcohol-Related Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Substance-Related Disorders; Alcoholism; Disease; Anxiety Disorders; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: NMCSD Oxytocin

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No