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

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ClinicalTrials.gov Identifier: NCT03036397
Recruitment Status : Completed
First Posted : January 30, 2017
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief 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.


Condition or disease Intervention/treatment Phase
Anxiety Disorder Fear Drug: SRX246 Drug: Placebo Phase 1

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of SRX246, a Vasopressin Receptor (V1a) Antagonist, on an Experimental Model of Fear and Anxiety in Humans
Actual Study Start Date : March 3, 2017
Actual Primary Completion Date : July 19, 2019
Actual Study Completion Date : July 19, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety
Drug Information available for: Vasopressin

Arm Intervention/treatment
Experimental: PLC then SRX
PLC for 5-7 days, then SRX246 for 5-7 days
Drug: SRX246
180mg qam/ 120mg qhs for 5-7 days

Drug: Placebo
twice daily for 5-7 days

Experimental: SRX then PLC
SRX246 for 5-7 days, then placebo for 5-7 days
Drug: SRX246
180mg qam/ 120mg qhs for 5-7 days

Drug: Placebo
twice daily for 5-7 days




Primary Outcome Measures :
  1. Fear and anxiety potentiated startle [ Time Frame: 5-7 days ]

Secondary Outcome Measures :
  1. Skin conductance [ Time Frame: 5-7 days ]
  2. Subjective Anxious Mood [ Time Frame: 5-7 days ]
  3. Latency of emotion recognition [ Time Frame: 5-7days ]
  4. Accuracy of emotion recognition [ Time Frame: 5-7days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03036397


Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Christian Grillon, Ph.D. National Institute of Mental Health (NIMH)

Additional Information:
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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT03036397     History of Changes
Other Study ID Numbers: 170046
17-M-0046
First Posted: January 30, 2017    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 19, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
Anxiety
Vasopressin
Fear-Potentiated Startle
Shock Threat
Emotion Recognition

Additional relevant MeSH terms:
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Anxiety Disorders
Mental Disorders
Vasopressins
Arginine Vasopressin
SRX246
Hemostatics
Coagulants
Vasoconstrictor Agents
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action