Oxytocin Nasal Spray for PTSD
(CBCT-OT RCT Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: VA Office of Research and Development
Disqualifiers: Substance dependence, Psychotic disorder, Borderline personality, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?
Leveraging veterans' intimate relationships during treatment for posttraumatic stress disorder (PTSD) has the potential to concurrently improve PTSD symptoms and relationship quality. Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) is a manualized treatment designed to simultaneously improve PTSD and relationship functioning for couples in which one partner has PTSD. Although efficacious in improving PTSD, the effects of CBCT on relationship satisfaction are small, especially among Veterans. Pharmacological augmentation of bCBCT with intranasal oxytocin, a neurohormone that influences mechanisms of trauma recovery and social behavior, may help improve the efficacy of bCBCT. The purpose of this randomized placebo-controlled trial is to compare the clinical and functional outcomes of bCBCT augmented with intranasal oxytocin (bCBCT + OT) versus bCBCT plus placebo (bCBCT + PL). The investigators will also explore potential mechanisms of action: communication, empathy, and trust.
Do I need to stop my current medications to join the trial?
The trial requires that you have been on a stable psychoactive medication regimen for at least 2 months, so you do not need to stop your current medications if they are stable.
What data supports the effectiveness of the drug oxytocin nasal spray for PTSD?
How does oxytocin nasal spray differ from other PTSD treatments?
Oxytocin nasal spray is unique because it delivers oxytocin directly to the brain, which may help reduce PTSD symptoms by affecting brain areas involved in fear and social behavior. This method is different from other treatments as it uses a nasal spray to target the brain more directly, potentially offering a new way to manage PTSD symptoms.13567
Eligibility Criteria
This trial is for veterans with PTSD who are in a relationship. It's designed to help improve both their PTSD symptoms and relationship quality. Participants must be willing to undergo couples therapy and use either an oxytocin or saline nasal spray.Inclusion Criteria
I have been on the same mental health medication for at least 2 months.
I am a veteran over 18 with PTSD diagnosed at least 3 months after my trauma.
I am over 18 and willing to join the study but I don't have PTSD.
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Exclusion Criteria
Imminent suicidality or homicidality in either member of the couple
Positive screen (7+) for borderline personality disorder (BPD) in either member of the couple as assessed by the MacLean Screening Instrument for BPD
Uncontrolled hypotension (systolic blood pressure <100 mm Hg) or hypertension (BP >160/100 mm Hg) as assessed by self-report and verified with VA chart review (in absence of chart documentation in past month, participant will be sent digital BP device and cuff to verify BP stability during video monitoring)
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) weekly, with either intranasal oxytocin or placebo administered prior to each session
8 weeks
8 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, with assessments at mid-treatment, post-treatment, 3-month, and 6-month intervals
6 months
Treatment Details
Interventions
- Intranasal Oxytocin (Hormone Therapy)
Trial OverviewThe study tests if adding oxytocin nasal spray to brief couples therapy (bCBCT) is more effective than just the therapy with a saline placebo. The goal is to see if this combination can better treat PTSD and enhance relationship satisfaction among veterans.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal OxytocinExperimental Treatment2 Interventions
Couples will receive Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) weekly. Prior to each session, the veteran participant will self-administer intranasal oxytocin.
Group II: Brief Cognitive Behavioral Conjoint Therapy for PTSD plus Intranasal PlaceboPlacebo Group2 Interventions
Couples will receive Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) weekly. Prior to each session, the veteran participant will self-administer intranasal placebo solution.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
VA San Diego Healthcare System, San Diego, CASan Diego, CA
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Who Is Running the Clinical Trial?
VA Office of Research and DevelopmentLead Sponsor
References
Augmenting Treatment for Posttraumatic Stress Disorder and Co-Occurring Conditions with Oxytocin. [2022]The goal of this manuscript is to review the extant literature examining the neurobiological and behavioral mechanisms underlying the potential utility of intranasal oxytocin as a novel pharmacologic intervention for the treatment of posttraumatic stress disorder (PTSD), and for the treatment of co-morbid PTSD and alcohol and substance use disorders.
Pilot test of intranasal oxytocin as an enhancer of brief couples therapy for posttraumatic stress disorder. [2023]Posttraumatic stress disorder (PTSD) negatively impacts military veterans and their intimate partners. Cognitive-Behavioral Conjoint Therapy (CBCT) was developed to address both PTSD and relationship satisfaction among couples. Although efficacious in improving PTSD, the effects of CBCT and the 8-session brief CBCT (bCBCT) on relationship satisfaction among veteran patients with PTSD are modest. Pharmacological augmentation with the neuropeptide oxytocin is promising for enhancing bCBCT's potency due to its effects on mechanisms of trauma recovery (e.g., extinction learning) and relationship functioning (e.g., trust, communication). The goal of this pilot uncontrolled clinical trial was to examine the feasibility and preliminary efficacy of bCBCT augmented with intranasal oxytocin for improving PTSD and relationship satisfaction among 10 U.S. veterans with PTSD and their intimate partners. Veterans self-administered 40 international units of intranasal oxytocin 30 min before each bCBCT session delivered to the couple via telehealth. Both partners completed pre-assessment, weekly, post, and 3-month follow-up assessments of PTSD symptoms and relationship satisfaction. Couples also provided qualitative feedback related to feasibility and engagement. Nine dyads completed the treatment. There were no serious adverse events. Veterans and partners reported moderate to large effect size improvements in relationship satisfaction (Hedge's g = 0.55 and 1.01, respectively). Veterans reported large effect size reductions in PTSD severity (Hedge's g = 1.87). These results suggest that virtual oxytocin-assisted bCBCT is feasible, scalable, potentially efficacious, and should be tested with a placebo-controlled randomized controlled trial.
Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals. [2020]Background: Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which develops in approximately 10% of trauma-exposed individuals. Currently, there are few early preventive interventions available for PTSD. Intranasal oxytocin administration early posttrauma may prevent PTSD symptom development, as oxytocin administration was previously found to beneficially impact neurobiological (e.g. amygdala reactivity) and socio-emotional PTSD vulnerability factors. Objective: The overall aim of this dissertation was to investigate the potential of intranasal oxytocin administration as early preventive intervention for PTSD. Methods: We performed a functional magnetic resonance imaging (fMRI) study to assess the acute effects of a single administration of oxytocin on the functional fear neurocircuitry - consisting of the amygdala and (pre)frontal brain regions - in recently trauma-exposed emergency department patients (range n = 37-41). In addition, we performed a multicentre randomized double-blind placebo-controlled clinical trial (RCT) to assess the efficacy of repeated intranasal oxytocin administration early after trauma for preventing PTSD symptom development up to six months posttrauma (n = 107). Results: In our fMRI experiments we observed acutely increased amygdala reactivity to fearful faces and attenuated amygdala-ventromedial and ventrolateral prefrontal cortex functional connectivity after a single oxytocin administration in recently trauma-exposed individuals. However, in our RCT we found that repeated intranasal oxytocin administration early posttrauma reduced subsequent PTSD symptom development in recently trauma-exposed emergency department patients with high acute PTSD symptoms. Conclusions: These findings indicate that repeated intranasal oxytocin is a promising early preventive intervention for PTSD for individuals at increased risk for PTSD due to high acute symptom severity. Administration frequency dependent effects of oxytocin or the effects of oxytocin administration on salience processing may serve as explanatory frameworks for the contrasting oxytocin effects on anxiety-related measures in our clinical and neuroimaging studies.
Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial. [2021]Posttraumatic stress disorder (PTSD) is the most highly prevalent mental health disorder among U.S. military Veterans. Prolonged Exposure (PE) therapy is one of the most widely used evidence-based treatments for PTSD, but there is substantial room for improvement in outcomes and retention rates. Accumulating data suggest that oxytocin offers a promising pharmacological approach towards achieving this goal. Therefore, the primary objective of this two-site Phase II study is to examine the ability of oxytocin (vs. placebo) administration combined with PE therapy to (1) reduce PTSD symptom severity, (2) accelerate the rate of PTSD symptom improvement, and (3) improve PE adherence and retention rates. To accomplish these objectives, we will employ a randomized, double-blind, placebo-controlled trial and use standardized, repeated dependent measures of change at five time points (baseline, mid-treatment, end of treatment, and 3 and 6 month follow-up). Intranasal oxytocin (40 IU) will be administered directly prior to each PE therapy session. Findings from this study will provide critical new information regarding the efficacy of oxytocin to augment psychosocial treatment for PTSD, as well as information regarding the physiological mechanisms underlying PTSD and positive treatment response. ClinicalTrials.gov Identifier: NCT04228289.
Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application. [2019]Oxytocin (OXT) is a cyclic nonapeptide, two amino acids of which are cysteine, forming an intramolecular disulfide bond. OXT is produced in the hypothalamus and is secreted into the bloodstream from the posterior pituitary. As recent studies have suggested that OXT is a neurotransmitter exhibiting central effects important for social deficits, it has drawn much attention as a drug candidate for the treatment of autism. Although human-stage clinical trials of the nasal spray of OXT for the treatment of autism have already begun, few studies have examined the pharmacokinetics and brain distribution of OXT after nasal application. The aim of this study is to evaluate the disposition, nasal absorption, and therapeutic potential of OXT after nasal administration. The pharmacokinetics of OXT after intravenous bolus injection to rats followed a two-compartment model, with a rapid initial half-life of 3 min. The nasal bioavailability of OXT was approximately 2%. The brain concentration of OXT after nasal application was much higher than that after intravenous application, despite much lower concentrations in the plasma. More than 95% of OXT in the brain was directly transported from the nasal cavity. The in vivo stress-relief effect by OXT was observed only after intranasal administration. These results indicate that pharmacologically active OXT was effectively delivered to the brain after intranasal administration. In conclusion, the nasal cavity is a promising route for the efficient delivery of OXT to the brain.
A Preliminary Examination of Endogenous Peripheral Oxytocin in a Pilot Randomized Clinical Trial of Oxytocin-Enhanced Psychotherapy for Posttraumatic Stress Disorder. [2022]Preclinical and clinical research suggests that the oxytocin system is implicated in the development and maintenance of stress and anxiety-related psychiatric conditions, such as posttraumatic stress disorder (PTSD). Recent research also suggests that intranasal oxytocin holds promise as a treatment for PTSD. However, little is known about the relationship between levels of peripheral oxytocin and PTSD symptom severity, PTSD treatment response, and repeated intranasal oxytocin administration.
CSF and blood oxytocin concentration changes following intranasal delivery in macaque. [2021]Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.