Study of the Effects of Oxytocin on Attentional Bias and Startle in PTSD

June 9, 2021 updated by: Steven Woodward, Palo Alto Veterans Institute for Research

Placebo-Controlled Study of the Effects of Oxytocin on Attentional Bias and Startle in PTSD

The investigators will test whether intranasal oxytocin (24 IU vs placebo) will induce effects on attention bias and startle comparable to those the investigators have shown to be induced by the presence (vs absence) of a service dog in Veterans diagnosed with PTSD. This possibility is suggested by a 2015 study showing that urinary oxytocin levels are elevated in association with mutual gaze between dogs and their owners.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background and significance:

Chronic severe posttraumatic stress disorder (PTSD) is among the most prevalent and expensive diagnoses addressed by the U.S. Army Medical Department and the Veterans Health Administration. While progress has been made in PTSD treatment, data from the World Mental Health Survey have recently shown that rates of recovery from combat-related PTSD, world-wide, are approximately one-half the rates of recovery from other trauma types. Furthermore, other recent studies have reported that effect sizes shown by evidence-based treatments for PTSD when applied to male patients are approximately half of what they are when applied to female patients. These results suggest the VA has far to go in achieving efficacious and effective behavioral treatments for this diagnosis affecting a large proportion of its patient population.

In the course of a DoD-funded study (Can a Canine Companion Modify Cardiac Autonomic Reactivity and Tone in PTSD) our laboratory has found that the presence of a service canine in the testing chamber in close proximity to the participant is associated with modification of visual attentional bias away from angry faces signalling social threat along with attenuation of autonomic responses to loud tones. The attenuation of bias towards social threat is of particular relevance to the social impairments seen in this disorder.Veterans with chronic severe PTSD frequently manifest impairments in the execution of key social roles such as those of spouse, parent and employee.

Service canine companionship and oxytocin (OT) appear to be on parallel tracks as novel candidate PTSD treatments or treatment enhancers. A wealth of anecdotal evidence has emerged from U.S. military clinical settings supporting the benefits of service canine companionship and canine-assisted interventions for military personnel with deployment-related mental health conditions; however, rigorously empirical support for this approach remains sparse. A growing literature exploring the role(s) of the OT system in PTSD now includes a number of encouraging findings. For example, in PTSD, OT modulates amygdala hemodynamic responses to emotional faces and increases anterior insula hemodynamic responses to social rewards. Intranasal OT administration normalizes amygdala functional connectivity in PTSD and increased subjective compassion for other persons. These findings align with findings in healthy persons. After intranasal administration, normal adults gaze more at the eye region of faces, have better memory for faces, are better able to infer the mental states of others, have more positive communications, are more generous, rate faces as more trustworthy owe, and exhibit increased trust behavior. OT also attenuates startle in healthy persons, attenuates amygdala responses to fear-inducing stimuli, and inhibits the stress-responsive release of cortisol. In turn, the human findings generally agree with a large animal literature showing that OT plays an important role in social behaviors such as partner preference, social bonding, and social cognition, while OT dysregulation produces a variety of social impairments.

A recent study published in Science showing that urinary OT levels are elevated in association with mutual gaze between dogs and their owners suggests these two lines of research may be converged on the target of PTSD. The investigators will compare the pattern of results of tests of attention bias and startle induced by intranasal OT (vs placebo) to those the investigators have shown to be induced by the presence (vs absence) of a service dog in Veterans diagnosed with PTSD.

Specific Aim 1: To test the effects of a single-dose OT administration in adults with PTSD on the pattern of performance on a set of laboratory tasks which have previously been administered to similar persons who were or were not accompanied by a service canine on separate occasions.

Hypothesis 1: Following single-dose OT administration, participants will exhibit attenuation of attentional bias toward negatively-valenced content, in general, and toward facial cues denoting social threat, in particular.

Hypothesis 2: Following single-dose OT administration, participants will exhibit reduced cardioacceleratory responses to loud tones and attenuated autonomic responses to a math stressor.

Preliminary power calculations indicate that a sample of 40 subjects in this within-subjects design will yield excellent power to detect a medium size effect (Critical t(38) = 2.02, α = .05, 1- β = .90) for the primary attentional bias measures.

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Menlo Park, California, United States, 94025
        • VA Palo Alto Health Care System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • US military Veteran
  • Current posttraumatic stress disorder
  • Medically healthy

Exclusion Criteria:

  • DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder
  • Active drug or alcohol use disorder within past 90 days
  • Currently participating in a clinical drug trial
  • Regular nasal obstruction or nosebleeds (use of saline or nasal decongestant permitted if subject has transient cold only)
  • Active medical problems: unstable seizures, significant physical illness (e.g., serious liver, renal, or cardiac pathology)
  • Sensitivity to preservatives, in particular E 216, E 218, and chlorobutanol hemihydrate
  • Significant hearing or vision impairments
  • Habitually drinks large volumes of water

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Immediate Oxytocin
Participants randomly assigned to this arm will receive OT nasal spray (24 IU) at laboratory visit 1 and placebo nasal spray at visit 2. The order will be masked for participants and study staff.
Drug: Oxytocin
single-dose administration of OT nasal spray, complete computer-based tasks post-dose for approximately 1 hour
Other Names:
  • syntocinon
Drug: Placebos
single-dose administration of placebo nasal spray, complete computer-based tasks post-dose for approximately 1 hour
Placebo Comparator: Delayed Oxytocin
Participants randomly assigned to this arm will receive placebo nasal spray at laboratory visit 1 and OT nasal spray (24 IU) at visit 2. The order will be masked for participants and study staff.
Drug: Oxytocin
single-dose administration of OT nasal spray, complete computer-based tasks post-dose for approximately 1 hour
Other Names:
  • syntocinon
Drug: Placebos
single-dose administration of placebo nasal spray, complete computer-based tasks post-dose for approximately 1 hour

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in attentional bias
Time Frame: 1-2 weeks
Changes between oxytocin vs. placebo lab sessions in the asymmetric allocation of visual attention to one or another of a pair of visual stimuli presented simultaneously as quantified by gaze tracking
1-2 weeks
Change in startle response -heart rate
Time Frame: 1-2 weeks
Difference between oxytocin vs. placebo lab sessions in the magnitude of pre-to-post startle stimulus change in heart rate
1-2 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in startle response -EDA
Time Frame: 1-2 weeks
Difference between oxytocin vs. placebo lab sessions in the magnitude of pre-to-post startle stimulus change in AC-coupled electrodermal activity at the hand
1-2 weeks
Change in startle response -EMG
Time Frame: 1-2 weeks
Difference between oxytocin vs. placebo lab sessions in the magnitude of pre-to-post startle stimulus change in corrugator electromyography
1-2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Palo Alto Veterans Institute for Research

Investigators

  • Principal Investigator: Steven H Woodward, PhD, VA Palo Alto Health Care System

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2017

Primary Completion (Actual)

June 9, 2021

Study Completion (Actual)

June 9, 2021

Study Registration Dates

First Submitted

April 3, 2017

First Submitted That Met QC Criteria

July 5, 2017

First Posted (Actual)

July 7, 2017

Study Record Updates

Last Update Posted (Actual)

June 10, 2021

Last Update Submitted That Met QC Criteria

June 9, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WOS0022ADM

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Posttraumatic Stress Disorder

Clinical Trials on Oxytocin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in New Zealand

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe