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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03036397
• Other study ID #: 170046
• Secondary ID: 17-M-0046
• Status: Completed
• Phase: Phase 1
• Start date: March 3, 2017
• Est. completion date: July 19, 2019

Study information

• Verified date: September 24, 2019
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 19, 2019
• Est. primary completion date: July 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 50 Years

Eligibility

• INCLUSION CRITERIA:

• Healthy male and female volunteers, ages 21-50, inclusive.

• Subjects able to give their consent and have signed informed consent forms indicating that they understand the purpose and procedures of the study and are willing to participate in the study procedures and restrictions.

• Body mass index (BMI) of 18.5 to 34.0 kg/M(2), inclusive, and a total body weight of >50kg (110 pounds).

EXCLUSION CRITERIA:

• Non-English speakers

• Current or history of Axis I psychiatric disorder(s) as identified with the Structured Clinical Interview for DSM-IV-TR, non-patient edition (SCID-np) and clinical evaluation.

• Active or history of active suicidal ideation.

• Lifetime alcohol or drug dependence according to the Structured Clinical Interview for DSM-IV-TR, non-patient edition (SCID-np).

• All prescription and non-prescription medications and herbal remedies are prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication and until at least 7 days or 5 half-lives (whichever is longer) after last dose of study medication, except hormonal contraceptives in females.

• Subject is currently participating in another clinical trial in which (s)he is or will be exposed to an investigational or non-investigational drug or device, or has been exposed to an investigational or non-investigational drug or device within the preceding 14 days or 5 half-lives of the investigational or non-investigational drug (whichever is longer).

• Current evidence or history of significant medical illness or organic brain impairment, including syndrome of inappropriate antidiuretic hormone secretion (SIADH), diabetes insipidus (DI), stroke, epilepsy, CNS tumor, demyelinating disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment that would likely interfere with the action, absorption, distribution, metabolism, or excretion of SRX246, or influence psychophysiological responses.

• Any laboratory abnormality that in the investigators judgment is considered to be clinically significant (ECG, TSH, LFT, etc.).

• Abnormal urine specific gravity (below 1.00 or above 1.03) as documented by urine sample refractometry.

• Subject who has resting blood pressure outside of a systolic blood pressure range of 90-140 mmHg or a diastolic blood pressure outside a range of 50-90 mmHg on two consecutive measurements taken up to 10 minutes apart.

• Subject who has resting pulse rate greater than 100 bpm or less than 50 bpm on two consecutive measurements taken up to 10 minutes apart.

• Pregnancy, lactating/breastfeeding, or positive pregnancy test.*

• A history of anaphylaxis, or any known/suspected hypersensitivity to SRX246, or allergy to gelatin.

• Lack of measurable startle response (3 times the baseline EMG activity) for at least 5 of 9 startles used during the habituation visit.

• Subjects who would be noncompliant with the visit schedule or study procedures. Possible noncompliance may include planned vacations or planned hospitalizations during the study.

• Participants who are physically able to get pregnant and those who are able to father a child, unwillingness to use at least two effective birth control methods or remain completely abstinent from heterosexual Intercourse for 15 days prior to the time they enroll in the study, until 15 days after their last exposure to the study drug. Effective methods of contraception for this study include:

1. hormonal contraception (birth control pills, injected hormones or vaginal ring),

2. intrauterine device,

3. barrier methods (condom or diaphragm) combined with spermicide, and

4. surgical sterilization (hysterectomy, tubal ligation, or vasectomy).

• Employee of NIMH or an immediate family member who is a NIMH employee.

• A urine pregnancy test is performed at each visit. Since this test might not detect the very early stage of pregnancy (i.e. maximum of 10 day period between fertilization and implantation), women of child-bearing age are excluded from the study if they do not agree to above contraceptive measures.

Related Conditions & MeSH terms

• Anxiety Disorders
• Healthy Volunteers

Intervention

Drug:
• SRX246
180mg qam/ 120mg qhs for 5-7 days
• Placebo
twice daily for 5-7 days

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fear and anxiety potentiated startle	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.	End of study
Secondary	Skin conductance		5-7 days
Secondary	Subjective Anxious Mood		5-7 days
Secondary	Latency of emotion recognition		5-7days
Secondary	Accuracy of emotion recognition		5-7days

External Links

•   NIH Clinical Center Detailed Web Page