Trial Summary
What is the purpose of this trial?Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition that disproportionately affects Veterans. Prolonged Exposure (PE) therapy is a "gold standard" treatment for PTSD. However, approximately one-third of Veterans fail to receive an adequate dose of treatment because they prematurely drop out of PE therapy. There is also room to improve PE treatment outcomes. Consistent with the VA Office of Research and Development initiative to develop effective treatments for PTSD, the proposed randomized clinical trial will examine the ability of oxytocin (as compared with placebo) combined with PE to reduce PTSD symptom severity, improve the rate of PTSD symptom reduction, and to enhance PE treatment retention and adherence. This two-site study will leverage the investments made in the nationwide rollout off PE therapy and has the potential to significantly improve mental health care among Veterans, advance the science in this area, and identify mechanisms underlying positive PTSD treatment response. Participants may choose to complete this research study via home-based telemedicine (HBT) care (i.e. service delivery to patients in their homes using consumer friendly, video-conferencing technology). HBT sessions will be delivered via standard desk, laptop computer, tablet, or smartphone using VA approved applications. All procedures that take place via telemedicine will be performed and completed as though they were in-person/in-office
Is the drug oxytocin a promising treatment for PTSD?Yes, oxytocin is a promising drug for treating PTSD. It may help reduce PTSD symptoms, improve therapy outcomes, and enhance social interactions, making patients feel safer and more engaged in treatment.4691012
What safety data exists for oxytocin treatment in PTSD?The provided research does not contain any safety data for oxytocin or its related names (Pitocin, Syntocinon, Viatocinon, oxytocin, Placebo, Control, Dummy Treatment) in the context of PTSD treatment. The studies focus on palonosetron and its use in chemotherapy-induced nausea and vomiting, not on oxytocin.12357
What data supports the idea that Oxytocin for PTSD is an effective drug?The available research shows that oxytocin, when combined with Prolonged Exposure (PE) therapy, may help reduce PTSD symptoms and improve therapy adherence. In one study, veterans who used oxytocin reported lower PTSD and depression symptoms and better working relationships with their therapists, although these results were not statistically significant. Another study found that oxytocin helped improve PTSD symptoms and relationship satisfaction in veterans and their partners. These findings suggest that oxytocin could be a promising addition to existing PTSD treatments, but more research is needed to confirm its effectiveness.6891112
Do I have to stop taking my current medications for the trial?You don't have to stop taking your current medications, but you must be on a stable dose of any psychotropic medications for at least four weeks before starting the trial.
Eligibility Criteria
This trial is for Veterans with PTSD, who can consent and perform well on a mental status exam. They may have mood or anxiety disorders but not bipolar disorder or current severe suicidal thoughts. Stable psychotropic medication use is okay.Inclusion Criteria
I am mentally capable of understanding and participating in the trial.
I have been diagnosed with an anxiety disorder.
Treatment Details
The study tests if oxytocin can improve PTSD symptoms and treatment retention in Veterans undergoing Prolonged Exposure therapy, compared to a placebo. Participants can join sessions via telemedicine using VA approved apps.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: OxytocinExperimental Treatment1 Intervention
40 IU intranasal oxytocin
Group II: PlaceboPlacebo Group1 Intervention
intranasal saline spray
Find a clinic near you
Research locations nearbySelect from list below to view details:
San Francisco VA Medical Center, San Francisco, CASan Francisco, CA
Ralph H. Johnson VA Medical Center, Charleston, SCCharleston, SC
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Who is running the clinical trial?
VA Office of Research and DevelopmentLead Sponsor
San Francisco VA Health Care SystemCollaborator
References
Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. [2022]Palonosetron (Aloxi(R), Onicit(R)) is a potent, single stereoisomeric 5-HT(3) receptor antagonist developed to prevent chemotherapy-induced nausea and vomiting. The pharmacokinetics and metabolic disposition of a single intravenous [(14)C]-palonosetron (10 microg/kg, 0.8 microCi/kg) bolus dose were evaluated in six healthy volunteers (three males, three females) using serial blood, plasma, urine and fecal samples obtained over 10 days. The safety, tolerability and cardiac effects were assessed. Radiolabeled metabolic characterization revealed that unchanged palonosetron accounted for 71.9% of the total radioactivity in plasma over 96 h, with an extensive distribution volume (8.34 l/kg) and mean plasma elimination half-life of 37 h. Approximately 83% of the dose was recovered in urine ( approximately 40% as unchanged drug, with 50% metabolized; M9 and M4 were the major metabolites) and 3.4% in feces. Hydrolysis of urine samples suggests that the metabolites are not beta-glucuronide or sulfate conjugates of the parent drug or metabolites. The blood to plasma concentration ratio of the total radioactivity was 1.2, on average, indicating little selective partitioning in erythrocytes. Palonosetron was generally well tolerated; headache was the most frequently reported adverse event. Electrocardiograms and 72 h Holter monitoring revealed no clinically significant changes. Palonosetron circulates in plasma mainly as the parent drug. Renal elimination is the primary excretion route, with parent drug and metabolites M9 and M4 accounting for the majority of palonosetron disposition. These results indicate that both renal and hepatic routes are involved in the elimination of palonosetron from the body.
Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant. [2018]The objective of this multicenter, phase II, open-label study was to evaluate the safety and efficacy of the newest 5-hydroxytryptamine3 (5-HT3) receptor antagonist, palonosetron, plus dexamethasone and aprepitant in preventing nausea and vomiting in patients receiving moderately emetogenic chemotherapy. Eligible patients received a single intravenous dose of palonosetron (0.25 mg on day 1 of chemotherapy), along with 3 daily oral doses of aprepitant (125 mg on day 1,80 mg on days 2 and 3) and dexamethasone (12 mg on day 1,8 mg on days 2 and 3). Efficacy and safety data were obtained from patient diaries and adverse event reporting. Fifty-eight patients were evaluable; 47% were women with breast cancer and 52% received cyclophosphamide-based chemotherapy. The proportion of patients with complete response (no emesis and no rescue medication) was 88% during the acute (0-24 hours) interval, 78% during the delayed (> 24-120 hours) interval, and 78% during the overall (0-120 hours post chemotherapy) interval. More than 90% of patients during all time intervals had no emetic episodes, and between 57% and 71% of patients reported no nausea during each of the 5 days post chemotherapy. Treatment was well tolerated, with no unexpected adverse events. These data demonstrate that palonosetron in combination with dexamethasone and aprepitant is safe and highly effective in preventing chemotherapy-induced nausea and vomiting in the days following administration of moderately emetogenic chemotherapy.
Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. [2018]Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient risk factors (female gender, younger age, alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine (5-HT)3 receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a clinical problem. A new agent, palonosetron, has recently been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. In a single dosing study, palonosetron was highly effective in controlling CINV compared with a single dose of dolasetron or ondansetron in patients receiving moderately emetogenic chemotherapy. Palonosetron in combination with dexamethasone demonstrated control of CINV in patients receiving highly emetogenic chemotherapy. Palonosetron appeared to be as effective in subsequent courses of chemotherapy compared with the initial course of chemotherapy. There were no clinically relevant differences seen among palonosetron, ondansetron or dolasetron in laboratory, electrocardiographic or vital-sign changes, and adverse reactions reported in the clinical trials were the most common reactions reported for the 5-HT3 receptor antagonist class. Recent studies using palonosetron-based anti-emetic combinations in moderately and highly emetogenic chemotherapy, as well as in the clinical setting of multiple-day chemotherapy, have been reported. Future studies may consider the use of palonosetron with current and other new agents and in other clinical settings, such as bone marrow transplantation and radiation therapy.
A psychobiological rationale for oxytocin in the treatment of posttraumatic stress disorder. [2019]Although cognitive-behavioral therapy (CBT) is an effective treatment for posttraumatic stress disorder (PTSD), many patients fail to attain remission with CBT. The authors propose augmentation of CBT with oxytocin in the treatment of PTSD. Oxytocin has a combination of pharmacologic effects that result in a "sense of safety" for the patient, which is a prerequisite to successful treatment of PTSD. We suggest a dual explanatory mechanism as to why oxytocin may be effective: through a reduction of fear response (decreasing amygdala activation, inhibiting fear response, and enhancing extinction learning) and through an increase of social interaction (activating social reward-related brain regions increasing engagement in the therapeutic alliance). Given that PTSD is marked by deficits in anxiety/stress regulation and in social functioning, and that oxytocin is implicated in both of these areas, oxytocin seems a likely candidate for treatment of patients with PTSD. Further clinical studies of the therapeutic value of oxytocin are indicated.
A prospective, randomized, double-blind, multicenter trial to evaluate the therapeutic efficacy and safety of palonosetron in the treatment of postoperative nausea and vomiting over a 72-h period. [2021]We performed a multicenter, randomized, double-blind trial to assess the efficacy and safety of a single, fixed, intravenous dose of palonosetron (0.075 mg) in the treatment of established postoperative nausea and vomiting (PONV).
Effects of systemic administration of oxytocin on contextual fear extinction in a rat model of post-traumatic stress disorder. [2021]One of the hallmark symptoms of posttraumatic stress disorder (PTSD) is the impaired extinction of traumatic memory. Single prolonged stress (SPS) has been suggested as an animal model of PTSD, since SPS rats exhibited the impaired fear extinction. Oxytocin (OXT) has been recently suggested as a potential pharmacotherapy for treatment of PTSD. In this study, using SPS rats we investigated the effects of multiple systemic administration of OXT on contextual fear extinction.
The role of netupitant and palonosetron in chemotherapy-induced nausea and vomiting. [2018]The combination of netupitant and palonosetron was approved by the Food and Drug Administration in October 2014 for the prevention of acute and delayed chemotherapy-induced nausea and vomiting associated with initial and repeat courses of moderately and highly emetogenic chemotherapy. Netupitant and palonosetron is available as a single capsule to be administered prior to each cycle of chemotherapy. The approval was based on phase II and III data in patients undergoing treatment with moderately and highly emetogenic chemotherapy. Netupitant and palonosetron's benefits include a convenient dosage form, dual-targeted mechanism, and favorable side effect profile, while its main limitations are cost and potential logistical issues surrounding administration. More studies are needed to adequately determine its role in therapy as well as which patients will derive the most benefit from its use.
Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial. [2019]Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition for which Prolonged Exposure (PE) therapy is highly efficacious. However, for some individuals, premature dropout and residual PTSD symptoms remain obstacles. The neuropeptide oxytocin is a promising candidate to enhance PE due to its ability to enhance 1) prosocial cognition and behavior, which are theorized to promote positive working alliance, and 2) extinction learning, which is the central mechanism of action underlying successful PE treatment. Despite a robust theoretical rationale, no studies to date have combined evidence-based psychotherapy for PTSD with oxytocin. This randomized, placebo-controlled, double-blind pilot trial examined the feasibility, safety, and preliminary efficacy of augmenting PE with oxytocin. Participants were 17 individuals with diverse index traumas. Participants self-administered intranasal oxytocin (40 IU) or matching placebo 45 min prior to each weekly PE therapy session. One adverse event occurred in the placebo group and three individuals dropped out (17.6%; 2 oxytocin group and 1 placebo group). The oxytocin group demonstrated lower PTSD and depression symptoms during PE, and had higher working alliance scores, although these differences did not reach statistical significance. Although preliminary, the findings support the feasibility of oxytocin combined with PE. Adequately powered studies are necessary to determine whether oxytocin enhances PE treatment outcomes and to examine potential mechanisms, such as accelerating extinction learning, enhancing early response, and preventing premature dropout. NCT03238924.
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.
[Oxytocin for the treatment of PTSD?] [2021]Oxytocin is mostly known for its pro-social effects and may increase positive emotions, and as such may be a relevant treatment option for PTSD. Although oxytocin indeed showed some alleviating effects on PTSD in the study by Koch et al., effects were small and the clinical significance of these findings remains to be determined.
Medication-Enhanced Psychotherapy for Posttraumatic Stress Disorder: Recent Findings on Oxytocin's Involvement in the Neurobiology and Treatment of Posttraumatic Stress Disorder. [2022]Traumatic experiences may result in Posttraumatic Stress Disorder (PTSD), which is characterized as an exaggerated fear response that cannot be extinguished over time or in safe environments. What are beneficial psychotherapeutic treatment options for PTSD patients? Can oxytocin (OXT), which is involved in the stress response, and safety learning, ameliorate PTSD symptomatology and enhance psychotherapeutic effects? Here, we will review recent studies regarding OXT's potential to enhance psychotherapeutic therapies for PTSD treatment.
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.