Oxytocin and Affect Processing in Posttraumatic Stress Disorder

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02546570
• Collaborator: National Center for PTSD (U.S. Fed)
• Enrollment: 11
• Location: 1
• Arms: 3
• Actual Duration (Months): 12
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Posttraumatic Stress Disorder (PTSD)	Drug: Oxytocin; Drug: Placebo	Phase 2

Detailed Description

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). The investigators expect oxytocin (compared to placebo) to positively influence affect processing in healthy subjects, as well as among those diagnosed with PTSD. Given current literature, the investigators expect oxytocin to elevate the processing\perception of positive-related stimuli, and reduce the salience of aversive or un-pleasant cues. The investigators expect oxytocin to impact participants' brain function as measured with functional magnetic resonance imaging (fMRI) while visually processing social and affect-related stimuli, rendering brain function and affective processing to be "more typical" or "adaptive" compared to placebo. Oxytocin's effect on human repertoire is not necessarily direct, but can interact with the individual's socioemotional characteristics, early life environment, and psychiatric symptoms. Therefore, the investigators will incorporate measures that capture the various dimensions that likely shape the effect of oxytocin.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Posttraumatic Stress Disorder and Affective Functioning: A Test of the Potentially Normalizing Effects of Oxytocin
• Actual Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Healthy adult controls (18-55) 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; See arm/group descriptions for dosage amount and procedure.; Other Names: Pitocin ; Drug: Placebo; See arm/group descriptions for dosage amount and procedure.; Other Names: saline
Experimental: Adults with PTSD (18-55) 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; See arm/group descriptions for dosage amount and procedure.; Other Names: Pitocin ; Drug: Placebo; See arm/group descriptions for dosage amount and procedure.; Other Names: saline
Experimental: Trauma-exposed/no-PTSD adults (18-55) 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; See arm/group descriptions for dosage amount and procedure.; Other Names: Pitocin ; Drug: Placebo; See arm/group descriptions for dosage amount and procedure.; Other Names: saline

Outcome Measures

Primary Outcome Measures

1. fMRI Analysis: Change in Anterior Insula Region [1 week; fMRI data collected at second and third visits, one week apart]

   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.

2. fMRI Analysis: Change in Accumbens Region [1 week; fMRI data collected at second and third visits, one week apart]

   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.

3. fMRI Analysis: Change in Amygdala Region [1 week; fMRI data collected at second and third visits, one week apart]

   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.

4. fMRI Analysis: Change in dACC Region [1 week; fMRI data collected at second and third visits, one week apart]

   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.

5. fMRI Analysis: Change in mOFC Region [1 week; fMRI data collected at second and third visits, one week apart]

   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.

6. fMRI Analysis: Change in rACC Region [1 week; fMRI data collected at second and third visits, one week apart]

   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.

7. fMRI Analysis: Change in vmPFC Region [1 week; fMRI data collected at second and third visits, one week apart]

   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.

Secondary Outcome Measures

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]

   Expect within-session (30 min) increase in peripheral salivary oxytocin level during OT sessions (within-session), and higher OT levels in oxytocin administration vs. placebo sessions. Peripheral OT levels measured with Salivettes (sterile cotton participants will be asked to chew on for 1 minutes).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06520

Sponsors and Collaborators

• Yale University
• National Center for PTSD

Investigators

• Principal Investigator: Linda Mayes, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02546570
• Other Study ID Numbers: 1502015347
• First Posted: Sep 11, 2015
• Last Update Posted: Apr 8, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Oxytocin

Study Results

Participant Flow

Arm/Group Title	Adults With PTSD (18-55)	Trauma-exposed/No-PTSD Adults (18-55)
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.
Period Title: Overall Study
STARTED	9	2
Crossover Order: Oxytocin, Placebo	6	2
Crossover Order: Placebo, Oxytocin	3	0
COMPLETED	9	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Adults With PTSD (18-55)	Trauma-exposed/No-PTSD Adults (18-55)	Total
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	Total of all reporting groups
Overall Participants	9	2	11
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	9 100%	2 100%	11 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	9 100%	2 100%	11 100%

Outcome Measures

1. Primary Outcome

Title	fMRI Analysis: Change in Anterior Insula Region
Description	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.
Time Frame	1 week; fMRI data collected at second and third visits, one week apart

Outcome Measure Data

Analysis Population Description

Data for all enrolled are summarized.

Arm/Group Title	Adults With PTSD (18-55): Drug	Adults With PTSD (18-55): Placebo	Adults Without PTSD (18-55): Drug	Adults Without PTSD (18-55): Placebo
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.
Measure Participants	9	9	2	2
forearm	-12.6	-1.6	10.6	-7.8
palm	-13.9	3.9	5.9	3.6

2. Primary Outcome

Title	fMRI Analysis: Change in Accumbens Region
Description	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.
Time Frame	1 week; fMRI data collected at second and third visits, one week apart

Outcome Measure Data

Analysis Population Description

Data for all enrolled are summarized.

Arm/Group Title	Adults With PTSD (18-55): Drug	Adults With PTSD (18-55): Placebo	Adults Without PTSD (18-55): Drug	Adults Without PTSD (18-55): Placebo
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.
Measure Participants	9	9	2	2
forearm	7.6	-7.9	-17.2	-12.7
palm	-14.8	-8.0	-8.5	1.2

3. Primary Outcome

Title	fMRI Analysis: Change in Amygdala Region
Description	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.
Time Frame	1 week; fMRI data collected at second and third visits, one week apart

Outcome Measure Data

Analysis Population Description

Data for all enrolled are summarized.

Arm/Group Title	Adults With PTSD (18-55): Drug	Adults With PTSD (18-55): Placebo	Adults Without PTSD (18-55): Drug	Adults Without PTSD (18-55): Placebo
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.
Measure Participants	9	9	2	2
forearm	-3.8	-9.1	14.5	-6.7
palm	-4.2	.58	16.7	-.45

4. Primary Outcome

Title	fMRI Analysis: Change in dACC Region
Description	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.
Time Frame	1 week; fMRI data collected at second and third visits, one week apart

Outcome Measure Data

Analysis Population Description

Data for all enrolled are summarized.

Arm/Group Title	Adults With and Without PTSD (18-55): Drug	Adults With and Without PTSD (18-55): Placebo	Adults Without PTSD (18-55): Drug	Adults Without PTSD (18-55): Placebo
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.
Measure Participants	9	9	2	2
forearm	-20.9	-16.4	-4.8	-30.2
palm	-23.8	-7.5	-10.9	-12.7

5. Primary Outcome

Title	fMRI Analysis: Change in mOFC Region
Description	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.
Time Frame	1 week; fMRI data collected at second and third visits, one week apart

Outcome Measure Data

Analysis Population Description

Data for all enrolled are summarized.

Arm/Group Title	Adults With PTSD (18-55): Drug	Adults With PTSD (18-55): Placebo	Adults Without PTSD (18-55): Drug	Adults Without PTSD (18-55): Placebo
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.
Measure Participants	9	9	2	2
forearm	1.5	2.5	1.7	-8.1
palm	-4.9	12.3	4.2	10.3

6. Primary Outcome

Title	fMRI Analysis: Change in rACC Region
Description	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.
Time Frame	1 week; fMRI data collected at second and third visits, one week apart

Outcome Measure Data

Analysis Population Description

Data for all enrolled are summarized.

Arm/Group Title	Adults With PTSD (18-55): Drug	Adults With PTSD (18-55): Placebo	Adults Without PTSD (18-55): Drug	Adults Without PTSD (18-55): Placebo
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.
Measure Participants	9	9	2	2
forearm	-5.9	-4.4	-0.2	-16.3
palm	-9.2	0.7	-1.6	-7.6

7. Primary Outcome

Title	fMRI Analysis: Change in vmPFC Region
Description	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.
Time Frame	1 week; fMRI data collected at second and third visits, one week apart

Outcome Measure Data

Analysis Population Description

Data for all enrolled are summarized.

Arm/Group Title	Adults With and Without PTSD (18-55): Drug	Adults With and Without PTSD (18-55): Placebo	Adults Without PTSD (18-55): Drug	Adults Without PTSD (18-55): Placebo
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.
Measure Participants	9	9	2	2
forearm	-3.8	-6.8	-3.3	-16.0
palm	-12.0	2.4	-2.8	-10.4

8. Secondary Outcome

Title	Salivary Oxytocin
Description	Expect within-session (30 min) increase in peripheral salivary oxytocin level during OT sessions (within-session), and higher OT levels in oxytocin administration vs. placebo sessions. Peripheral OT levels measured with Salivettes (sterile cotton participants will be asked to chew on for 1 minutes).
Time Frame	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

Outcome Measure Data

Analysis Population Description

Saliva samples were collected as outlined. The research team attempted to analyze them. However, despite best efforts, and assurances from the manufacturer, the assay performance remained unacceptable primarily in regards to inadequate sensitivity and significant variability in sample duplicates. Therefore, there are no results to report.

Arm/Group Title	Adults With PTSD (18-55): Drug	Adults With PTSD (18-55): Placebo	Adults Without PTSD (18-55): Drug	Adults Without PTSD (18-55): Placebo
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.
Measure Participants	0	0	0	0

Adverse Events

Arm/Group Title	Adults With PTSD (18-55)		Trauma-exposed/No-PTSD Adults (18-55)
Arm/Group Description	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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.		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). Oxytocin: See arm/group descriptions for dosage amount and procedure. Placebo: See arm/group descriptions for dosage amount and procedure.
All Cause Mortality
	Adults With PTSD (18-55)		Trauma-exposed/No-PTSD Adults (18-55)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/2 (0%)
Serious Adverse Events
	Adults With PTSD (18-55)		Trauma-exposed/No-PTSD Adults (18-55)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Adults With PTSD (18-55)		Trauma-exposed/No-PTSD Adults (18-55)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.