Acute Anxiolytic Effects of Riluzole on Subjects With Social Anxiety Disorder

Social Anxiety Disorder Clinical Trial

Official title:

Double-Blind, Placebo-Controlled, Single-Dose Crossover Study Examining the Effects of Sublingual Riluzole (BHV-0223) on Public Speaking in Social Anxiety Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03017508
• Other study ID #: 1605017768
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 2017
• Est. completion date: January 29, 2021

Study information

• Verified date: April 2021
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of the current proposal is to examine if sublingual riluzole can reduce anxiety in people with social anxiety disorder during a public speaking task.

Description:

The investigators propose conducting a double-blind, placebo controlled crossover study examining the effects of BHV-0223 on public speaking anxiety. Twenty participants with DSM-5 defined social anxiety disorder and clinically significant public speaking anxiety on the Impromptu Speech Task will be enrolled in a challenge study. Participants will be given BHV-0223 (or placebo) under double-blind crossover conditions 1 hour prior to performing each of 2 impromptu speech tasks. The two study days involving BHV-0223 (or placebo) administration and impromptu speech task will be separated by 2 to 10 days to allow for medication washout. There will be a final follow-up visit 2 to 10 days later to perform a complete Physical exam and do follow-up liver function testing and a Complete Blood Count. Our primary outcome will examine BHV-0223's effects (compared to placebo) on self-rated anxiety during the impromptu speech task. The investigators will also collect physiological measures of anxiety, clinician-rated measures of anxiety, and measures of speech performance as secondary outcomes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 29, 2021
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male or female (post-menopausal, surgically sterile, or negative pregnancy test at screening and agreement to utilize an established birth control, including complete abstinence, during the testing period) between the age of 18 and 65 yrs.

2. Meet DSM-5 criteria for social anxiety disorder by structured clinical interview (SCID) and have a LSAS public speaking subscale score >6.

3. Stable psychiatric medications. Participants must have had stable doses of all psychiatric medications for the month prior to treatment and have been on stable doses of SSRI and antidepressants for at least 1 month prior to study enrollment. As needed benzodiazepine use will be permitted as long as subjects refrain from using benzodiazepines for the 48 hours prior to the study.

4. Medically and neurologically healthy on the basis of physical examination, SMAC-20 (including LFT's, TFT's), VDRL, CBC w/ diff, urinalysis, urine toxicology, EKG, and medical history. Individuals with stable medical problems that do not have CNS effects or interfere with medications administered (e.g., oral hypoglycemics) may be included if their medications have not been adjusted in the month prior to entry;

5. Urine toxicology screen negative for drug of abuse.

6. Able to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines.

Exclusion Criteria:

1. Positive pregnancy test

2. Breastfeeding females

3. History of substance abuse disorder (ETOH, cocaine, opiates, PCP) within the last 6 months or positive urine toxicology on screening (within the previous 6 months).

4. History of pervasive developmental disorder or psychotic disorder by DSM-IV-TR criteria.

5. Presence of dentures, braces, piercings at the time of dosing, or any physical findings in the mouth or tongue that, in the opinion of the Principal Investigator, would be likely to interfere with successful completion of the dosing procedure.

6. Participants with a medical condition that might interfere with the physiological absorption and motility (ie, gastric bypass, duodenectomy) or gastric bands.

7. Participants with any clinically significant abnormality or abnormal laboratory test results.

8. Participant has a current diagnosis of viral hepatitis (HBsAG or HVC) or a history of liver disease.

9. Participant has significant history of seizure disorder other than a single childhood febrile seizure (eg. Epilepsy)

10. Participant using any drugs known to induce or inhibit CYP 1A2 metabolism (examples of inducers: rifampin, carbamazepine, etc.; examples of inhibitors: fluvoxamine, ciprofloxacin, fluoroquinolones, etc.) within 30 days prior to the first study drug administration.

11. Participants with a history of allergic reactions to riluzole or other related drugs.

12. Participant has a history of anaphylaxis, a documented hypersensitivity reaction, or a clinically important reaction to any drug.

13. Participant has received another investigational drug or device within the 30 days (90 days for biologics) prior to the first dosing or is currently participating in an investigational study involving no drug administration.

14. Participant with clinically significant electrocardiogram (ECG) abnormalities (QTcF >450 msec) or vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 50 or over 100 bpm) at Screening or Baseline (Day -1).

15. Any reason which, in the opinion of the Principal Investigator, would prevent the participant from being in the study.

Related Conditions & MeSH terms

• Anxiety Disorders
• Disease
• Performance Anxiety
• Phobia, Social
• Social Anxiety Disorder

Intervention

Drug:
• BHV-0223
35mg of sublingual riluzole before performing an anxiety provoking speech task. Participants will then be clinically assessed every hour for 3 hours.
• Placebo
a sublingual tablet identical to the active drug will be given before performing an anxiety provoking speech task. Participants will then be clinically assessed every hour for three hours.

Locations

Country	Name	City	State
United States	Connecticut Mental Health Center	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Biohaven Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (6)

Baker SL, Heinrichs N, Kim HJ, Hofmann SG. The liebowitz social anxiety scale as a self-report instrument: a preliminary psychometric analysis. Behav Res Ther. 2002 Jun;40(6):701-15. — View Citation

Davidson JR. Use of benzodiazepines in social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder. J Clin Psychiatry. 2004;65 Suppl 5:29-33. Review. — View Citation

Mathew SJ, Amiel JM, Coplan JD, Fitterling HA, Sackeim HA, Gorman JM. Open-label trial of riluzole in generalized anxiety disorder. Am J Psychiatry. 2005 Dec;162(12):2379-81. — View Citation

Pittenger C, Coric V, Banasr M, Bloch M, Krystal JH, Sanacora G. Riluzole in the treatment of mood and anxiety disorders. CNS Drugs. 2008;22(9):761-86. Review. — View Citation

Ries BJ, McNeil DW, Boone ML, Turk CL, Carter LE, Heimberg RG. Assessment of contemporary social phobia verbal report instruments. Behav Res Ther. 1998 Oct;36(10):983-94. — View Citation

Sanacora G, Kendell SF, Levin Y, Simen AA, Fenton LR, Coric V, Krystal JH. Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol Psychiatry. 2007 Mar 15;61(6):822-5. Epub 2006 Dec 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	VAS-anxiety Immediately After the Impromptu Speech Task	Measure Description: In the Visual Analogue Scale (VAS) participants are presented with a straight horizontal line of 100 mm in length and asked to mark the placement that would best describe the intensity of the anxiety felt at that moment. The left end (0mm) represents "no anxiety" and the right end (100mm) represents "the worst anxiety ever felt" by the participant.The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks, generating a numerical score along a continuum	up to 60 minutes