Oxytocin and Affect Processing in Posttraumatic Stress Disorder

NCT02546570 | Completed Phase 2 Results

• 1 other identifier: 1502015347
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will use multiple methods (including Oxytocin intranasal inhalation, neuroimaging, behavioral measures, peripheral hormone measurements) to examine how individuals' behavior, cognition, and brain function is impacted by the neuro-hormone Oxytocin. Specifically, the investigators plan to evaluate the influence of Oxytocin administration on affective processing in non-trauma exposed and trauma-exposed adults (both with and without posttraumatic stress disorder, PTSD).

Conditions

Posttraumatic Stress Disorder (PTSD)

Outcome Measures

Primary Outcomes (7)

• fMRI Analysis: Change in Anterior Insula Region

  Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.

  1 week; fMRI data collected at second and third visits, one week apart

• fMRI Analysis: Change in Accumbens Region

  Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.

  1 week; fMRI data collected at second and third visits, one week apart

• fMRI Analysis: Change in Amygdala Region

  Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.

  1 week; fMRI data collected at second and third visits, one week apart

• fMRI Analysis: Change in dACC Region

  Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.

  1 week; fMRI data collected at second and third visits, one week apart

• fMRI Analysis: Change in mOFC Region

  Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.

  1 week; fMRI data collected at second and third visits, one week apart

• fMRI Analysis: Change in rACC Region

  Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.

  1 week; fMRI data collected at second and third visits, one week apart

• fMRI Analysis: Change in vmPFC Region

  Change in blood-oxygen-level dependent (BOLD) contrast signal in regions of interest relevant to fear/threat (e.g., decrease in amygdala activation) and reward processing (increase in ventral striatum activation) in oxytocin versus placebo sessions. Forearm brush stroking targets C-tactile (CT) nerves, which respond to gentle touch and engage the insula and cortical brain regions that mediate social-emotional processing. Palm brush stroking is the control condition, in that CT afferents do not innervate the palm. We contrasted BOLD responses to gentle continuous brushing of the arm vs. palm (4 blocks of 8 trials each), expecting greater oxytocin-related increases in brain reactivity within the insula and other regions in the forearm condition versus the palm condition. The values are % signal change from baseline.

  1 week; fMRI data collected at second and third visits, one week apart

Secondary Outcomes (1)

• Salivary Oxytocin

  Within session (30 min) and between sessions (1 week); saliva samples collected twice (before and after OT administration) at both second and third visits, one week apart

Study Arms (3)

Healthy adult controls (18-55)

EXPERIMENTAL

Drug: oxytocin and placebo nasal spray (within-subjects design, blinded and counterbalanced for two lab sessions); dosage=24 international units (IU). Participant inserts nasal spray container 1cm into nostril at angle of 45 degrees and sprays. Will wait 15 seconds then repeat administration to other nostril (alternating between nostrils). Participants will receive 6 puffs in total (3 in each nostril).

Drug: Oxytocin; Drug: Placebo

Adults with PTSD (18-55)

EXPERIMENTAL

Drug: oxytocin and placebo nasal spray (within-subjects design, blinded and counterbalanced for two lab sessions); dosage=24 international units (IU). Participant inserts nasal spray container 1cm into nostril at angle of 45 degrees and sprays. Will wait 15 seconds then repeat administration to other nostril (alternating between nostrils). Participants will receive 6 puffs in total (3 in each nostril).

Drug: Oxytocin; Drug: Placebo

Trauma-exposed/no-PTSD adults (18-55)

EXPERIMENTAL

Drug: oxytocin and placebo nasal spray (within-subjects design, blinded and counterbalanced for two lab sessions); dosage=24 international units (IU). Participant inserts nasal spray container 1cm into nostril at angle of 45 degrees and sprays. Will wait 15 seconds then repeat administration to other nostril (alternating between nostrils). Participants will receive 6 puffs in total (3 in each nostril).

Drug: Oxytocin; Drug: Placebo

Interventions

Oxytocin DRUG

See arm/group descriptions for dosage amount and procedure.

Also known as: Pitocin

Adults with PTSD (18-55); Healthy adult controls (18-55); Trauma-exposed/no-PTSD adults (18-55)

Placebo DRUG

See arm/group descriptions for dosage amount and procedure.

Also known as: saline

Adults with PTSD (18-55); Healthy adult controls (18-55); Trauma-exposed/no-PTSD adults (18-55)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults: age 18-55
• Be in good medical health
• Be cooperative with testing
• English is a language spoken in the family
• PTSD as diagnosed by a certified clinician or the research team for PTSD group.

You may not qualify if:

• Moderate or severe acute or chronic medical illnesses (e.g.cardiac disease, diabetes, epilepsy, influenza).
• History of hypertension with baseline blood pressure above 160 mm Hg (systolic) over 100 mm Hg (diastolic).
• history of syncope and/or baseline blood pressure below 100 mm Hg (systolic).
• weight \>300lb
• The use of some psychotropic medications will not be allowed. Females taking contraceptive hormones will not be able to participate in the study.
• Currently breast feeding or pregnant
• For MRI ONLY: Any metal or electromagnetic implants
• For MRI ONLY: Significant hearing loss or other severe sensory impairment
• A fragile health status.
• For MRI ONLY: A history of seizures or current use of anticonvulsants
• Healthy adult controls (HC):
• Be free of both neurological and psychiatric disorders (current and past) on the basis of self-report
• Be free of psychiatric disorders

Sponsors & Collaborators

• Yale University: lead
• National Center for PTSD: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Oxytocin; Sodium Chloride

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Lauren Sippel
• Organization: National Center for PTSD

lauren.m.sippel@dartmouth.edu

802-295-9363

Study Officials

• Linda Mayes, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2015
• First Posted: September 11, 2015
• Study Start: August 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: April 8, 2020
• Results First Posted: April 8, 2020

Record last verified: 2020-03

Locations

US (1)