Sex/Gender Differences in Risk and Resilience to PTSD; Implication of Oxytocin

• Sponsor: Megan Moran-Santa Maria (Other)
• Overall Status: Completed
• CT.gov ID: NCT01963078
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arms: 4
• Duration (Months): 21
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The purpose of the study is to use fMRI to investigate amygdala response to fearful faces in men and women with and without PTSD who have experienced childhood trauma. The study will also compare the effects of oxytocin and placebo on amygdala response, and explore the interaction of oxytocin plasma levels and amygdala response in men and women with and without PTSD who have experienced childhood trauma.

Hypothesis 1: Amygdala responding will be greater in subjects with PTSD as compared to resilient subjects, and no sex differences in the magnitude of the response will be found.

Hypothesis 2A: In response to OT, women will exhibit a greater reduction in amygdala responding than men.

Hypothesis 2B: In response to OT, women with PTSD will exhibit a greater reduction in amygdala responding compared to women without PTSD.

Hypothesis 3A: Women with PTSD will have lower levels of plasma OT as compared to men with PTSD, and women and men without PTSD.

Hypothesis 3B: Plasma OT levels will be inversely correlated with amygdala responding to fearful faces in women but not in men.

Condition or Disease	Intervention/Treatment	Phase
PTSD	Drug: Oxytocin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Sex/Gender Differences in Risk and Resilience to PTSD; Implication of Oxytocin
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: PTSD placebo Day 1, Oxytocin Day 2 Participants PTSD will self-administer matching placebo (containing all ingredients except OT) at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005).	Drug: Placebo; Other Names: Saline
Experimental: PTSD Oxytocin Day 1, Placebo Day 2 Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005).	Drug: Oxytocin; Other Names: Pitocin
Placebo Comparator: Resilient Placebo Day 1, Oxytocin Day 2 Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005).	Drug: Placebo; Other Names: Saline
Experimental: Resilient Oxytocin Day 1, Placebo Day 2 Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m.on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005).	Drug: Oxytocin; Other Names: Pitocin

Outcome Measures

Primary Outcome Measures

1. Change in Amygdala Activation- Oxy Minus Placebo [Days 1 and 2]

   Bold signal response to facial recognition task was contrasted between oxytocin and saline administrations. Participants with PTSD and Resilient Controls each underwent 2 sets of scanning procedures, one with placebo and one with Oxytocin. Participants were randomly assigned to received Oxytocin on Day 1 or Day 2, and placebo on the opposite day, to mitigate crossover effects. Outcome measure is change in bold signal response between the two days; bold signal response on placebo was subtracted from bold signal response on Oxytocin to obtain change score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Ages 18-60.

2. Subjects scoring moderate to severe (>3) on a minimum of one of the five trauma domains of the Childhood Trauma Questionnaire.

3. Subjects must have experienced, witnessed, or confronted an event(s) that involved actual or threatened death or serious injury, or a threat to the physical integrity of themselves, or others and the person's response involved intense fear, helplessness, and/or horror (Criterion A DSM-IV for PTSD), prior to the age of 18.

Exclusion Criteria

1. Subjects with evidence of or a history of head trauma, neurological disorders, seizures, unconsciousness or any other major medical disorder.

2. Subjects with current (past 90 days) psychotic disorder or bipolar affective disorder.

3. Subjects with any psychoactive substance abuse within the last 30 days as evidenced by subject report or urine drug screen.

4. Women who are pregnant or nursing.

5. Women who are post-menopausal or have had a full hysterectomy.

6. Subjects who have a BMI greater than 35.

7. Subjects who are unwilling to maintain abstinence from alcohol and caffeine for the 24-hour period prior to the study visits and from illicit drug use for the 72 hour period prior to study visits.

8. Persons with ferrous metal implants or pacemaker.

9. Subjects who are claustrophobic.

10. Subjects taking endocrine or cardiovascular medications (other than blood pressure medications) during the 30-day period prior to the study.

11. Subjects with a postive breathalyzer or urine drug screen. Group - Specific Inclusion/Exclusion Criteria Individuals with PTSD Inclusion Criteria

12. Subjects must meet DSM-IV criteria for current (i.e. last 6 months) PTSD. 2. Subjects may also meet criteria for a mood disorder (except bipolar affective disorder, see Exclusion Criteria) or other anxiety disorders (panic disorder, agoraphobia, social phobia, generalized anxiety disorder, or obsessive compulsive disorder) or past (>90 days) alcohol dependence. The inclusion of subjects with affective and other anxiety disorders is essential because of the marked frequency of the co-existence of mood and other anxiety disorders among patients with PTSD (Brady, Killeen, Brewerton, & Lucerini, 2000; Kessler, Chiu, Demler, Merikangas, & Walters, 2005).

Exclusion Criteria

1. As above.

2. Substance dependence within the past year, except for nicotine or alcohol. Resilient Controls Inclusion Criteria

3. As above. Exclusion Criteria

4. Subjects meeting criteria for current or past (i.e. last 90 days) Axis I mood or anxiety disorders (including PTSD and depression).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Neurosciences Division-Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Megan Moran-Santa Maria

Investigators

• Principal Investigator: Megan Moran- Santa Maria, PhD, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Megan Moran-Santa Maria, Assistant Professor, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT01963078
• Other Study ID Numbers: 1R21MH099619-01
• First Posted: Oct 16, 2013
• Last Update Posted: Dec 11, 2018
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Oxytocin

Study Results

Participant Flow

Recruitment Details	Participants were recruited primarily through media advertisements and flyers.

Arm/Group Title	PTSD Placebo Day 1, Oxytocin Day 2	PTSD Oxytocin Day 1, Placebo Day 2	Resilient Placebo Day 1, Oxytocin Day 2	Resilient Oxytocin Day 1, Placebo Day 2
Arm/Group Description	Participants PTSD will self-administer matching placebo (containing all ingredients except OT) at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo	Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin	Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo	Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin
Period Title: Overall Study
STARTED	9	10	10	9
COMPLETED	8	9	9	7
NOT COMPLETED	1	1	1	2

Baseline Characteristics

Arm/Group Title	PTSD Placebo Day 1, Oxytocin Day 2	PTSD Oxytocin Day 1, Placebo Day 2	Resilient Placebo Day 1, Oxytocin Day 2	Resilient Oxytocin Day 1, Placebo Day 2	Total
Arm/Group Description	Participants PTSD will self-administer matching placebo (containing all ingredients except OT) at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo	Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin	Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo	Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin	Total of all reporting groups
Overall Participants	9	10	10	9	38
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	9 100%	10 100%	10 100%	9 100%	38 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 55.6%	5 50%	5 50%	7 77.8%	22 57.9%
Male	4 44.4%	5 50%	5 50%	2 22.2%	16 42.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	1 11.1%	1 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	3 33.3%	3 30%	2 20%	3 33.3%	11 28.9%
White	6 66.7%	7 70%	8 80%	5 55.6%	26 68.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants) [Number]
United States	9 100%	10 100%	10 100%	9 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	Change in Amygdala Activation- Oxy Minus Placebo
Description	Bold signal response to facial recognition task was contrasted between oxytocin and saline administrations. Participants with PTSD and Resilient Controls each underwent 2 sets of scanning procedures, one with placebo and one with Oxytocin. Participants were randomly assigned to received Oxytocin on Day 1 or Day 2, and placebo on the opposite day, to mitigate crossover effects. Outcome measure is change in bold signal response between the two days; bold signal response on placebo was subtracted from bold signal response on Oxytocin to obtain change score.
Time Frame	Days 1 and 2

Outcome Measure Data

Analysis Population Description

Population analyzed are participants who completed both scans and had usable MRI data.

Arm/Group Title	PTSD Placebo Day 1, Oxytocin Day 2	PTSD Oxytocin Day 1, Placebo Day 2	Resilient Placebo Day 1, Oxytocin Day 2	Resilient Oxytocin Day 1, Placebo Day 2
Arm/Group Description	Participants PTSD will self-administer matching placebo (containing all ingredients except OT) at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo	Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin	Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo	Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin
Measure Participants	8	9	9	7
Mean (Standard Deviation) [percentage of BOLD signal change]	-0.01 (0.36)	-0.02 (0.41)	0.05 (0.54)	0.21 (0.33)

Adverse Events

Time Frame	Adverse events were collected for each participant under both conditions, placebo and Oxytocin. Adverse events are reported summarily for each group.
Arm/Group Title	PTSD Placebo		PTSD Oxytocin		Resilient Placebo		Resilient Oxytocin
Arm/Group Description	Participants PTSD will self-administer matching placebo (containing all ingredients except OT) at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo		Participants with PTSD will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin		Resilient controls will self-administer matching placebo spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Placebo		Resilient controls will self-administer 24 IUs of OT nasal spray at 10:30 a.m. on Day 1 of study procedures, approximately 45-minutes prior the scanning sessions. This dose and timing of administration were selected based on similar fMRI studies (Domes, et al., 2007; Domes, et al., 2010; Kirsch, et al., 2005). Oxytocin
All Cause Mortality
	PTSD Placebo		PTSD Oxytocin		Resilient Placebo		Resilient Oxytocin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)		0/19 (0%)		0/19 (0%)
Serious Adverse Events
	PTSD Placebo		PTSD Oxytocin		Resilient Placebo		Resilient Oxytocin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)		0/19 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	PTSD Placebo		PTSD Oxytocin		Resilient Placebo		Resilient Oxytocin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)		0/19 (0%)		0/19 (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.