Oxytocin Suppresses Substance Use Disorders Associated With Chronic Stress

• Sponsor: Jennifer Mitchell (Other)
• Overall Status: Completed
• CT.gov ID: NCT02742532
• Collaborator: United States Naval Medical Center, San Diego (U.S. Fed), United States Department of Defense (U.S. Fed), Congressionally Directed Medical Research Programs (U.S. Fed), Eisenhower Army Medical Center (U.S. Fed)
• Enrollment: 63
• Location: 1
• Arms: 2
• Actual Duration (Months): 26.3
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder; Stress Disorders, Post-Traumatic; Anxiety Disorders; Substance Use Disorders	Drug: Oxytocin; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: Oxytocin Suppresses Substance Use Disorders Associated With Chronic Stress
• Actual Study Start Date: Apr 20, 2017
• Actual Primary Completion Date: Jul 1, 2019
• Actual Study Completion Date: Jul 1, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Craving to Use Alcohol Rating (Visual Analog Scale) [Change from baseline to post-drug at 20 minutes]

   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.

Secondary Outcome Measures

1. Change in Stress Rating (Visual Analog Scale) [Change from baseline to post-drug at 20 minutes]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Naval Medical Center San Diego	San Diego	California	United States	92106

Sponsors and Collaborators

• Jennifer Mitchell
• United States Naval Medical Center, San Diego
• United States Department of Defense
• Congressionally Directed Medical Research Programs
• Eisenhower Army Medical Center

Investigators

• Principal Investigator: Mardi Smith, PhD, United States Naval Medical Center, San Diego

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 5, 2019

More Information

Publications

None provided.

• Responsible Party: Jennifer Mitchell, Associate Professor, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02742532
• Other Study ID Numbers: NMCSD Oxytocin
• First Posted: Apr 19, 2016
• Last Update Posted: Oct 19, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Disease; Substance-Related Disorders; Alcoholism; Anxiety Disorders; Stress Disorders, Post-Traumatic; Oxytocin

Study Results

Participant Flow

Arm/Group Title	Oxytocin	Placebo
Arm/Group Description	Intra-nasal oxytocin (40 IUs; 5 puffs in each nostril) Oxytocin: Intranasal oxytocin 40 IU	Intra-nasal saline placebo (5 puffs in each nostril) Placebo: Intranasal saline solution
Period Title: Overall Study
STARTED	31	32
COMPLETED	28	31
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Oxytocin	Placebo	Total
Arm/Group Description	Intra-nasal oxytocin (40 IUs; 5 puffs in each nostril) Oxytocin: Intranasal oxytocin 40 IU	Intra-nasal saline placebo (5 puffs in each nostril) Placebo: Intranasal saline solution	Total of all reporting groups
Overall Participants	31	32	63
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	31 100%	32 100%	63 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	27.09	27.38	27.24
Sex: Female, Male (Count of Participants)
Female	5 16.1%	3 9.4%	8 12.7%
Male	26 83.9%	29 90.6%	55 87.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.2%	1 3.1%	2 3.2%
Asian	0 0%	1 3.1%	1 1.6%
Native Hawaiian or Other Pacific Islander	2 6.5%	1 3.1%	3 4.8%
Black or African American	2 6.5%	0 0%	2 3.2%
White	25 80.6%	29 90.6%	54 85.7%
More than one race	1 3.2%	0 0%	1 1.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	31 100%	32 100%	63 100%
Self-Reported Alcoholic drinks per week (standard drinks/week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [standard drinks/week]	51.2 (39.9)	43.9 (45.9)	47.4 (42.9)

Outcome Measures

1. Primary Outcome

Title	Change in Craving to Use Alcohol Rating (Visual Analog Scale)
Description	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.
Time Frame	Change from baseline to post-drug at 20 minutes

Outcome Measure Data

Analysis Population Description

All subjects who completed this outcome measure were included.

Arm/Group Title	Oxytocin	Placebo
Arm/Group Description	Intra-nasal oxytocin (40 IUs; 5 puffs in each nostril) Oxytocin: Intranasal oxytocin 40 IU	Intra-nasal saline placebo (5 puffs in each nostril) Placebo: Intranasal saline solution
Measure Participants	29	32
Mean (Standard Deviation) [score on a scale]	0.076 (1.77)	-0.928 (1.42)

2. Secondary Outcome

Title	Change in Stress Rating (Visual Analog Scale)
Description	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.
Time Frame	Change from baseline to post-drug at 20 minutes

Outcome Measure Data

Analysis Population Description

All subjects who completed this outcome measure were included.

Arm/Group Title	Oxytocin	Placebo
Arm/Group Description	Intra-nasal oxytocin (40 IUs; 5 puffs in each nostril) Oxytocin: Intranasal oxytocin 40 IU	Intra-nasal saline placebo (5 puffs in each nostril) Placebo: Intranasal saline solution
Measure Participants	29	32
Mean (Standard Deviation) [score on a scale]	-0.755 (1.24)	-1.268 (1.82)

Adverse Events

Time Frame	From enrollment through study completion, an average of 1 year
Arm/Group Title	Oxytocin		Placebo
Arm/Group Description	Intra-nasal oxytocin (40 IUs; 5 puffs in each nostril) Oxytocin: Intranasal oxytocin 40 IU		Intra-nasal saline placebo (5 puffs in each nostril) Placebo: Intranasal saline solution
All Cause Mortality
	Oxytocin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/32 (0%)
Serious Adverse Events
	Oxytocin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Oxytocin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/32 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.