A proof-of-concept randomized crossover clinical trial of a first-in-class vasopressin 1a receptor antagonist for PTSD: Design, methods, and recruitment.

Background: Almost eight million Americans suffer from Posttraumatic Stress Disorder (PTSD). Current PTSD drug therapies rely on repurposed antidepressants and anxiolytics, which produce undesirable side effects and have recognized compliance issues. Vasopressin represents a promising and novel target for pharmacological intervention. Logistical issues implementing a clinical trial for a novel PTSD pharmaceutical are relatively uncharted territory as trials concerning a new agent have not been published in the past several decades. All published trials have repurposed FDA-approved psychoactive medications with known risk profiles. Our recruitment challenges are discussed in this context.
Methods: An 18-week proof-of-concept randomized crossover clinical trial of a first-in-class vasopressin 1a receptor antagonist (SRX246) for PTSD was conducted. All participants received SRX246 for 8 weeks, the placebo for 8 weeks, and the drug vs. placebo arms were compared. Participants were assessed every 2 weeks for PTSD symptoms as well as other medication effects. Results were expected to provide an initial demonstration of safety and tolerability in this clinical population and potentially clinical efficacy in SRX246-treated patients measured by Clinician Administered PTSD Scale (CAPS) score changes, clinical impression, and other indices compared to placebo. The primary hypothesis was that SRX246 would result in a clinically meaningful 10-point reduction in mean CAPS score compared to placebo.
Discussion: This study is the first to investigate an oral vasopressin 1a receptor antagonist for PTSD. As a wave of PTSD clinical trials with new pharmaceutical compounds are beginning now, lessons learned from our recruitment challenges may be invaluable to these endeavors.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors, with the exception of Dr. Difede, Dr. Simon, Ms. Damiano, Ms. Itzkowitz, Dr. Lu, Dr. Brownstein, and Dr. Spielman, declare no conflicts of interest. Dr. Difede has funding from Department of Defense Clinical Trial Grant (No. W81XWH-18-1-0262), and Weill Cornell Medical College. Dr. Difede serves as a member of the advisory board at Pear Therapeutics, Inc. Dr. Simon and Dr. Brownstein serve as officers at Azevan Pharmaceuticals, Inc., and hold equity in the company. Dr. Spielman served as a paid consultant to Azevan Pharmaceuticals, Inc. for this project. Dr. S. Lu is an employee, holds equity, and receives compensation. Ms. E. Damiano is an officer and receives compensation; Ms. D. Itzkowitz is an employee and receives compensation.
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