Effects of SRX246, a Vasopressin Receptor (V1a) Antagonist, on an Experimental Model of Fear and Anxiety in Humans

Healthy Volunteers Clinical Trial

Official title: Effects of SRX246, a Vasopressin Receptor (V1a) Antagonist, on an Experimental Model of Fear and Anxiety in Humans

Status Completed

Clinical Trial Summary

Background:

Arginine vasopressin (AVP) is a hormone made in the body. It can make negative feelings stronger. The way AVP is regulated may be abnormal in people who have mood and anxiety disorders. SRX246 is a new drug that can block a receptor for AVP on brain cells. Researchers want to study how this drug affects the way people respond to threat and anxiety.

Objectives:

To see if the new drug SRX246 affects how people respond to the threat of an unpleasant shock.

Eligibility:

Healthy adults ages 21-50

Design:

Participants will be screened in another protocol.

Participants will have 4 visits over 4 weeks.

At visit 1, participants will have small electrodes taped to their arm to give shocks. Electrodes on the arm, chest, and face will measure sweat, heart rate, and blinking. Participants will hear loud noises and get test shocks for about 15 minutes.

At the other 3 visits, participants will have some or all of these tests:

• Blood and urine tests

• Heart tests

• Suicide screen

At each visit, participants will answer questions about their mood and anxiety. They will identify emotions in pictures. They will have shock testing for 40 minutes: they will hear loud sounds through headphones and get shocks.

Participants will take the study pill 2 times a day for a week after visit 1 and a week after visit 3. One week it will be SRX246. The other week it will be a placebo.

Participants may be contacted daily to remind them to take the medicine.

Participants will have either a follow-up visit or follow-up phone call.

Clinical Trial Description

Objective: The objective of this proposal is to determine the effects of SRX246, a candidate anxiolytic and investigational new drug, on fear and anxiety based on fear-potentiated startle in humans. Additionally, the effects of the compound on emotion recognition will be explored. The compound is a first-in-class, highly selective, orally available, CNS penetrating vasopressin (V1a) receptor antagonist developed by Azevan Pharmaceuticals Inc. The anti-fear and anti-anxiety activity twice daily dosing for 10-14 doses over 5-7 days of SRX246 will be evaluated in healthy male and female subjects using a behavioral paradigm of phasic (fear) and sustained (anxiety) aversive states derived from experimental models in humans and pre-clinical studies in rodents. Subjects will also undergo a computerized behavioral task assessing neurocognitive processing of emotions.

Study population: The study population will consist of up to 47 healthy male and female volunteers between the ages of 21-50 with diverse racial and ethnic backgrounds.

Design: The study will use a double-blind, cross-over design in which each subject will receive placebo and 180 mg every morning/120 mg every evening (total 300mg every day) of SRX246 for a total of 10-14 doses over 5-7 days before testing (given in counter-balanced order). We will examine the effect of the drug on the potentiation of startle using a well-established paradigm that involves anticipation of no-shock, predictable shock, and unpredictable shock. Drug effects on emotion recognition will also be explored.

Outcome measures: The main outcome measures for the startle potentiation task are the magnitude of the startle reflex and retrospective anxiety during each condition; secondary measures are skin conductance and subjective anxiety. Latency and accuracy of emotion recognition will be measured in the Emotional Expression Multimorph Task. ;

Related Conditions & MeSH terms

• Anxiety Disorders
• Healthy Volunteers

• NCT number: NCT03036397
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: March 3, 2017
• Completion date: July 19, 2019