Ketamine Infusion for Social Anxiety Disorder

NCT02083926 | Completed Early Phase 1 Results

• 1 other identifier: 1310012947
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

• Social Anxiety Disorder (SAD) is common and causes significant impairment.
• First-line treatments for Social Anxiety Disorder are only partially effective. Many SAD patients experience little or inadequate symptom relief with available treatments.
• Ketamine is a potent NMDA receptor antagonist. Ketamine represents an agent with a potentially novel mechanism of action for the treatment of anxiety disorders.
• Ketamine has demonstrated efficacy in the treatment of psychiatric disorders closely related to Social Anxiety Disorder including Major Depression, Bipolar Depression and possibly Obsessive-Compulsive Disorder. Ketamine represents the possibility to provide rapid symptom relief to patients with SAD and may provide the mechanism for future drug development to treat SAD more rapidly and effectively.

Conditions

Social Anxiety Disorder

Keywords

Social Anxiety Disorder; SAD; Ketamine

Outcome Measures

Primary Outcomes (2)

• Visual Analogue Scale for Anxiety Symptoms (VAS-anxiety)

  Instrument that tries to measure anxiety, that is believed to range across a continuum of values and cannot easily be directly measured.We used a straight horizontal line of 100 mm in length. The ends were defined as the extreme limits of the parameter to be measured (anxiety); oriented from the left (no anxiety) to the right (worst anxiety ever felt). The patient marks on the line the point that they feel represents their perception of their current state.The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks. We examined Visual Analog Scale (VAS) for anxiety symptoms at screening, 1 hour prior to infusion, 1, 2 and 3 hours after infusion, 1, 2, 3, 5, 7, 10, and 14 days following a single ketamine/saline infusion.

  Day 1 (1+28)

• Liebowitz Social Anxiety Score (LSAS)

  Clinician-administered scale for the assessment of fear and avoidance found in social phobia (SAD); it has 24 items divided into 2 subscales, 13 for performance anxiety, and 11 for social situations each rated from 0 to 3 (0=none,1=mild,2=moderate,3=definite). The sum scores for Fear and Avoidance results in an overall score (max 144 points). There are 4 clinician subscales: fear of social interaction, fear of performance, avoidance of social interaction and avoidance of performance 0 to 30= SAD is unlikely 30 to 60=SAD is probable 60 to 90=SADis very probable \>90= SAD highly probable

  Day 1 (1+28)

Study Arms (2)

Ketamine infusion

EXPERIMENTAL

A ketamine infusion was given on day 0 (28) at a dose of 0.5mg/kg over 40 minutes. Assessments were conducted pre-infusion, 3-h post-infusion, and days 1 (1+28), 2 (2+28), 3 (3+28), 5 (5+28), 7 (7+28), 10 (10+28) and 14 (14+28) post-infusion.

Drug: Ketamine

Saline infusion

EXPERIMENTAL

A saline infusion was given on day 0 (28) at a dose of 0.5mg/kg over 40 minutes. Assessments were conducted pre-infusion, 3-h post-infusion, and days 1 (1+28), 2 (2+28), 3 (3+28), 5 (5+28), 7 (7+28), 10 (10+28) and 14 (14+28) post-infusion.

Other: Saline

Interventions

Ketamine DRUG

Ketamine (a single 0.5mg/kg intravenously over 40 minutes).

Also known as: Ketalar

Ketamine infusion

Saline OTHER

Saline (a single 0.5mg/kg intravenously over 40 minutes).

Also known as: Placebo

Saline infusion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult between the ages of 18 and 65 years
• Meet DSM IV criteria for Social Anxiety Disorder by structured clinical interview (SCID) and have a LSAS \>60 with or without co-morbid MDD

You may not qualify if:

• Positive pregnancy test
• History of substance abuse disorder within the last 6 months or positive urine toxicology on screening (within the previous 6 months).
• History of pervasive developmental disorder or psychotic disorder by DSM-IV-TR criteria
• Medical comorbidity that significantly increases the risks associated with ketamine infusion (e.g. untreated hypertension, significant cardiovascular disease)

Sponsors & Collaborators

• Yale University: lead
• Patterson Trust Mentored Research Award: Clinical, Health Services and Policy Research: collaborator

Study Sites (1)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Location

Related Publications (6)

• Abdallah CG, Averill LA, Collins KA, Geha P, Schwartz J, Averill C, DeWilde KE, Wong E, Anticevic A, Tang CY, Iosifescu DV, Charney DS, Murrough JW. Ketamine Treatment and Global Brain Connectivity in Major Depression. Neuropsychopharmacology. 2017 May;42(6):1210-1219. doi: 10.1038/npp.2016.186. Epub 2016 Sep 8.

  PMID: 27604566 BACKGROUND

• Aitken RC. Measurement of feelings using visual analogue scales. Proc R Soc Med. 1969 Oct;62(10):989-93. doi: 10.1177/003591576906201005. No abstract available.

  PMID: 4899510 BACKGROUND

• Davey HM, Barratt AL, Butow PN, Deeks JJ. A one-item question with a Likert or Visual Analog Scale adequately measured current anxiety. J Clin Epidemiol. 2007 Apr;60(4):356-60. doi: 10.1016/j.jclinepi.2006.07.015. Epub 2006 Dec 27.

  PMID: 17346609 BACKGROUND

• Freitas-Ferrari MC, Hallak JE, Trzesniak C, Filho AS, Machado-de-Sousa JP, Chagas MH, Nardi AE, Crippa JA. Neuroimaging in social anxiety disorder: a systematic review of the literature. Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30;34(4):565-80. doi: 10.1016/j.pnpbp.2010.02.028. Epub 2010 Mar 4.

  PMID: 20206659 BACKGROUND

• Glue P, Medlicott NJ, Harland S, Neehoff S, Anderson-Fahey B, Le Nedelec M, Gray A, McNaughton N. Ketamine's dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders. J Psychopharmacol. 2017 Oct;31(10):1302-1305. doi: 10.1177/0269881117705089. Epub 2017 Apr 26.

  PMID: 28441895 BACKGROUND

• Taylor JH, Landeros-Weisenberger A, Coughlin C, Mulqueen J, Johnson JA, Gabriel D, Reed MO, Jakubovski E, Bloch MH. Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial. Neuropsychopharmacology. 2018 Jan;43(2):325-333. doi: 10.1038/npp.2017.194. Epub 2017 Aug 29.

  PMID: 28849779 DERIVED

MeSH Terms

Conditions

Phobia, Social

Interventions

Ketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Phobic Disorders; Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

A significant limitation of our study was that 17 of 18 subjects correctly identified when they received ketamine, suggesting that the use of saline as a placebo control for ketamine led to inadequate blinding.

Results Point of Contact

• Title: Dr. Michael H. Bloch
• Organization: Yale University

michael.bloch@yale.edu

2037374539

Study Officials

• Michael H. Bloch, MD, MS

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2014
• First Posted: March 11, 2014
• Study Start: January 2, 2015
• Primary Completion: September 27, 2016
• Study Completion: September 27, 2016
• Last Updated: March 18, 2021
• Results First Posted: March 18, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)