Clinical trial NCT00989937
Conditions: Anxiety Disorders
Keywords: oxytocin
Sponsor: University of California, San Diego
Start date: 2009-02-01; Completion date: 2011-04-01
Enrollment: 17 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The objective of the study is to compare the efficacy of intranasal oxytocin versus intranasal placebo to improve anxiety symptoms in patients with a variety of anxiety disorders.

Detailed description:
Anxious patients treated with even the best currently available anti-anxiety drugs continue to experience significant symptoms.

A variety of basic science, animal studies, and human studies support the idea that the neuropeptide oxytocin may be effective against anxiety in humans. For example, plasma oxytocin levels may function as an index of central serotonin (5-HT) function in human subjects, and serotonin is well-known to be involved in clinical anxiety disorders. Since oxytocin is released directly from limbic-hypothalamic cells, this response presumably represents a direct central assessment of 5-HT response in limbic-hypothalamus (Lee 2003). In animal models, Ring 2006 examined the effects of oxytocin on both behavioral and autonomic parameters of the anxiety response in male mice using three pharmacologically validated preclinical models of anxiety: the four-plate test (FPT), elevated zero maze (EZM), and stress-induced hyperthermia (SIH). The results from this study provide specific behavioral and autonomic evidence of anxiolytic-like effects for oxytocin. In primates, Emiliano et al 2007 found support for the idea that that SSRIs' therapeutic effects on social affiliation and anxiety may be mediated in part through components of the oxytocin system. Human studies include Kosfeld et al (2005), who demonstrated that oxytocin administered intranasally to healthy human subjects in a double-blind, placebo controlled study increased levels of trust. As well, Kirsch et al (2005) showed that intranasal oxytocin reduced activation of brain circuits involved in fear in human subjects. Finally, Scantamburlo (2007) showed a significant negative correlation between oxytocin and the scored symptoms depression and anxiety. These studies clearly suggest the potential utility of OTR agonism as a therapeutically relevant mechanism of action for novel anxiolytics in both sexes.

Each subject will be enrolled for 6 week treatment period after a screening phase. Study procedures involve weekly clinic visits as an outpatient. Forty patients will be randomly assigned to either 40 International Units (IU) oxytocin twice daily or vehicle placebo. After 3 weeks, treatments will be crossed over such that subjects that received oxytocin will receive placebo and vice versa. The study ratio is 1:1. Dose of oxytocin is based upon previous studies in humans showing improvement in psychiatric populations related changes in behavior and brain function (Kosfeld et al, 2005; Kirsch 2005; Heinrich M 2003).

The total study duration for each individual subject will be approximately 7 weeks, which includes up to 21-day screening/wash-out period, a baseline (randomization) visit, three week treatment period, 1 week washout, baseline, and three weeks cross over treatment.

Arms: arm 1: 20 IU BID for the first week, 40 IU BID for the following two weeks, one week washout, 3 week placebo trial arm 2: Three week placebo trial, one week washout, 20 IU BID for the fifth week, 40 IU BID for the following two weeks
Interventions: intervention 1: Oxytocin intervention 2: Placebo
Intervention descriptions: intervention 1: 20 IU BID or 40 IU BID intervention 2: 20 IU BID or 40 IU BID

Protocol documents: