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

NCT01963078 | Completed Phase 2 Results DMC

• 1 other identifier: 1R21MH099619-01
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

PTSD

Outcome Measures

Primary Outcomes (1)

• Change in Amygdala Activation- Oxy Minus Placebo

  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.

  Days 1 and 2

Study Arms (4)

PTSD placebo Day 1, Oxytocin Day 2

PLACEBO COMPARATOR

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

PTSD Oxytocin Day 1, Placebo Day 2

EXPERIMENTAL

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

Resilient Placebo Day 1, Oxytocin Day 2

PLACEBO COMPARATOR

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

Resilient Oxytocin Day 1, Placebo Day 2

EXPERIMENTAL

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

Interventions

Oxytocin DRUG

Also known as: Pitocin

PTSD Oxytocin Day 1, Placebo Day 2; Resilient Oxytocin Day 1, Placebo Day 2

Placebo DRUG

Also known as: Saline

PTSD placebo Day 1, Oxytocin Day 2; Resilient Placebo Day 1, Oxytocin Day 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ages 18-60.
• Subjects scoring moderate to severe (\>3) on a minimum of one of the five trauma domains of the Childhood Trauma Questionnaire.
• 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.

You may not qualify if:

• Subjects with evidence of or a history of head trauma, neurological disorders, seizures, unconsciousness or any other major medical disorder.
• Subjects with current (past 90 days) psychotic disorder or bipolar affective disorder.
• Subjects with any psychoactive substance abuse within the last 30 days as evidenced by subject report or urine drug screen.
• Women who are pregnant or nursing.
• Women who are post-menopausal or have had a full hysterectomy.
• Subjects who have a BMI greater than 35.
• 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.
• Persons with ferrous metal implants or pacemaker.
• Subjects who are claustrophobic.
• Subjects taking endocrine or cardiovascular medications (other than blood pressure medications) during the 30-day period prior to the study.
• As above.
• \. Subjects meeting criteria for current or past (i.e. last 90 days) Axis I mood or anxiety disorders (including PTSD and depression).

Sponsors & Collaborators

• Megan Moran-Santa Maria: lead

Study Sites (1)

Clinical Neurosciences Division-Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Sippel LM, Flanagan JC, Holtzheimer PE, Moran-Santa-Maria MM, Brady KT, Joseph JE. Effects of intranasal oxytocin on threat- and reward-related functional connectivity in men and women with and without childhood abuse-related PTSD. Psychiatry Res Neuroimaging. 2021 Nov 30;317:111368. doi: 10.1016/j.pscychresns.2021.111368. Epub 2021 Aug 20.

  PMID: 34455213 DERIVED

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. Megan Moran-Santa Maria
• Organization: MUSC

moranm@musc.edu

843-817-6233

Study Officials

• Megan Moran- Santa Maria, PhD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: October 16, 2013
• Study Start: April 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: December 11, 2018
• Results First Posted: December 11, 2018

Record last verified: 2018-11

Locations

US (1)