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Ketamine Infusion for Social Anxiety Disorder

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ClinicalTrials.gov Identifier: NCT02083926
Recruitment Status : Unknown
Verified July 2016 by Yale University.
Recruitment status was:  Active, not recruiting
First Posted : March 11, 2014
Last Update Posted : July 12, 2016
Sponsor:
Collaborator:
Patterson Trust Awards Program in Clinical Research
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE March 5, 2014
First Posted Date  ICMJE March 11, 2014
Last Update Posted Date July 12, 2016
Study Start Date  ICMJE March 2014
Estimated Primary Completion Date March 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2014)
Visual Analog Scale (VAS) of Anxiety States [ Time Frame: First 2 weeks following infusion ]
We will examine Visual Analog Scale (VAS) of Anxiety States ratings of anxiety intensity 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 7, 2014)
Visual Analog Scale (VAS) of Anxiety States [ Time Frame: First 2 weeks following infusion ]
We will examine Visual Analog Scale (VAS) of Anxiety States ratings of anxiety intensity at baseline, 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2014)
  • Anxiety Severity [ Time Frame: First 2 weeks following infusion ]
    We will examine Beck Anxiety Inventory (BAI) ratings of anxiety severity at screening, 1 hour prior to infusion, 3 hours after infusion, 1, 2, 3, 5, 7, 10, and 14 days following a single ketamine/saline infusion.
  • Depression Severity [ Time Frame: First 2weeks following infusion ]
    We will examine Hamilton Depression Rating scale (HAM-D) ratings of depression severity at screening, 1 hour prior to infusion, 3 hours after infusion, 1, 2, 3, 5, 7, 10, and 14 days following a single ketamine/saline infusion.
  • Clinical Global Impressions [ Time Frame: First 2 weeks following infusion ]
    We will examine Clinical Global Impressions (CGI) ratings of overall severity of SAD symptoms at screening, 1 hour prior to infusion, 3 hours after infusion, 1, 7 and 14 days following a single ketamine/saline infusion.
  • Brief Psychiatric Rating Scale, Positive Symptom Subscale (BPRS-PS) [ Time Frame: First 2 weeks following infusion ]
    We will examine Brief Psychiatric Rating Scale, Positive Symptom Subscale (BPRS-PS) ratings of thought content, conceptual disorganization, hallucinatory behavior, and grandiosity at screening, 1 hour prior to infusion,1-3 hours after infusion, 1 day following a single ketamine/saline infusion.
  • Clinician-Administered Dissociative States Scale [ Time Frame: First 2 weeks following infusion ]
    We will examine Clinician-Administered Dissociative States Scales (CADSS) ratings of dissociative symptoms at screening, 1 hour prior to infusion, 3 hours after infusion, 1 day following a single ketamine/saline infusion.
  • Self-Statement During Public Speaking Scale (SPSS) [ Time Frame: First week following infusion ]
    We will examine Self-Statement During Public Speaking Scale (SPSS) ratings of cognitions that occurred during a speech 1 hour prior to infusion, 3 hours after infusion, 1, 7, and days following a single ketamine/saline infusion.
  • Impromptu Speech Behavioral Assessment Test [ Time Frame: First 2 weeks following infusion ]
    We will examine the Impromptu Speech Behavioral Assessment Test (BAT) of social anxiety symptoms during public speaking at 1 hour prior to infusion, 1 and 7 days following a single ketamine/saline infusion.
  • Attention Bias [ Time Frame: First 2 weeks following infusion ]
    We will examine attention bias on the dot-probe paradigm 1 hour before infusion, 3 hours after infusion, 1, 2, 3, 5, 7, 10 and 14 days following a single ketamine/saline infusion.
  • SAD Severity [ Time Frame: First 2 weeks following infusion ]
    We will examine the Liebowitz Social Anxiety Scale (LSAS) ratings of SAD severity at screening, 1 hour before infusion, 3 hours after infusion, 1, 2, 3, 5, 7, 10 and 14 days following a single ketamine/saline infusion.
  • Positive and Negative Affect Symptoms [ Time Frame: First Week following infusion ]
    We will examine positive and negative affect schedule (PANAS) ratings of positive and negative symptoms at screening, 1 hour before infusion, 1 and 7 days following a single ketamine/saline infusion.
  • State-Trait Anxiety Inventory [ Time Frame: First 2 Weeks Following Infusion ]
    We will examine State-Trait Anxiety Inventory (STAI) ratings of trait and state anxiety at screening, 1 hour before infusion, 3 hours after infusion, 1, 2, 3, 5, 7, 10 and 14 days following a single ketamine/saline infusion.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2014)
  • Anxiety Severity [ Time Frame: First 2 weeks following infusion ]
    We will examine Hamilton Anxiety Rating scale (HAM-A) ratings of anxiety severity at baseline, 1 hour prior to infusion, 3 hours after infusion, 1, 2, 3, 5, 7, 10, and 14 days following a single ketamine/saline infusion.
  • Depression Severity [ Time Frame: First 2weeks following infusion ]
    We will examine Hamilton Depression Rating scale (HAM-D) ratings of depression severity at baseline, 1 hour prior to infusion, 3 hours after infusion, 1, 2, 3, 5, 7, 10, and 14 days following a single ketamine/saline infusion.
  • Clinical Global Impressions [ Time Frame: First 2 weeks following infusion ]
    We will examine Clinical Global Impressions (CGI) ratings of overall severity of SAD symptoms at baseline, 1 hour prior to infusion, 3 hours after infusion, 1, 7 and 14 days following a single ketamine/saline infusion.
  • Brief Psychiatric Rating Scale, Positive Symptom Subscale (BPRS-PS) [ Time Frame: First 2 weeks following infusion ]
    We will examine Brief Psychiatric Rating Scale, Positive Symptom Subscale (BPRS-PS) ratings of thought content, conceptual disorganization, hallucinatory behavior, and grandiosity at baseline, 1 hour prior to infusion, 3 hours after infusion, 1 day following a single ketamine/saline infusion.
  • Clinician-Administered Dissociative States Scale [ Time Frame: First 2 weeks following infusion ]
    We will examine Clinician-Administered Dissociative States Scales (CADSS) ratings of dissociative symptoms at baseline, 1 hour prior to infusion, 3 hours after infusion, 1 day following a single ketamine/saline infusion.
  • Visual Analog Scale (VAS) of Anxiety States [ Time Frame: First 2 Weeks Following Infusion ]
    We will examine Visual Analog Scale (VAS) of Anxiety States ratings of anxiety intensity at baseline, 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.
  • Self-Statement During Public Speaking Scale (SPSS) [ Time Frame: First 2 weeks following infusion ]
    We will examine Self-Statement During Public Speaking Scale (SPSS) ratings of cognitions that occurred during a speech at baseline, 1 hour prior to infusion, 3 hours after infusion, 1, 7, and 14 days following a single ketamine/saline infusion.
  • Impromptu Speech Behavioral Assessment Test [ Time Frame: First 2 weeks following infusion ]
    We will examine the Impromptu Speech Behavioral Assessment Test (BAT) of social anxiety symptoms during public speaking at 1 hour prior to infusion, 3 hours after infusion, 1, 7 and 14 days following a single ketamine/saline infusion.
  • Heart Rate Variability (HRV) [ Time Frame: First 2 weeks following infusion ]
    We will examine heart rate variability (hrv) before, during and after impromptu speeches 1 hour before infusion, 3 hours after infusion, 1, 7 and 14 days after a single ketamine/saline infusion.
  • Respiratory Sinus Arrhythmia (RSA) [ Time Frame: First 2 weeks following infusion ]
    We will examine respiratory sinus arrhythmia (RSA) before, during and after impromptu speeches 1 hour before infusion, 3 hours after infusion, 1, 7 and 14 days after a single ketamine/saline infusion.
  • Heart rate (HR) [ Time Frame: First 2 weeks following infusion ]
    We will examine heart rate (HR) before, during and after impromptu speeches 1 hour before infusion, 3 hours after infusion, 1, 7 and 14 days following a single ketamine/saline infusion.
  • Skin Conductance (SC) [ Time Frame: First 2 weeks following infusion ]
    We will examine skin conductance (SC) before, during and after impromptu speeches 1 hour before infusion, 3 hours after infusion, 1, 7 and 14 days after a single ketamine/saline infusion.
  • Attention Bias [ Time Frame: First 2 weeks following infusion ]
    We will examine attention bias on the dot-probe paradigm 1 hour before infusion, 3 hours after infusion, 1, 2, 3, 5, 7, 10 and 14 days following a single ketamine/saline infusion.
  • SAD Severity [ Time Frame: First 2 weeks following infusion ]
    We will examine the Liebowitz Social Anxiety Scale (LSAS) ratings of SAD severity at baseline, 1 hour before infusion, 3 hours after infusion, 1, 2, 3, 5, 7, 10 and 14 days following a single ketamine/saline infusion.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine Infusion for Social Anxiety Disorder
Official Title  ICMJE Ketamine Infusion for Social Anxiety Disorder
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.

Detailed Description

Roughly one-third to one-half of patients with generalized SAD do not experience significant clinical benefit from current evidence-based treatment for SAD such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or venlafaxine and cognitive behavioral therapy (CBT). Failure of anxiety relief in patients with SAD is a source of substantial morbidity, distress, and decreases in quality of life. Novel pharmacological treatments are needed to improve patient outcomes with SAD.

Converging lines of evidence from neuroimaging and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of SAD. In a Magnetic Resonance Spectroscopy (MRS) study, an elevated glutamate to creatinine ratio was found in the anterior cingulate cortex of SAD patients when compared to healthy controls. Elevated thalamic glutamine levels have been demonstrated in patients with SAD. Pre-clinical rodent studies have also established a strong link between glutamate regulation and anxiety.

Ketamine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor, a major type of glutamate receptor in the brain. Ketamine is routinely used for anesthetic induction because of its dissociative properties. However in research studies, ketamine is effective treatment in reducing symptoms in depressive and possibly anxiety disorders. In multiple controlled clinical studies, ketamine has produced a rapid antidepressant effect in unipolar and bipolar depression. Ketamine's anti-depressant effects peak 1-3 days following infusion. Ketamine's antidepressant effect is observed long after ketamine has been metabolized and excreted by the body and after ketamine's sedative and dissociative effects have dissipated.

The results of several clinical studies suggest that ketamine may also have significant anxiolytic effects. Patients with major depressive disorder given a single ketamine infusion have shown strong and significant reductions in comorbid anxiety symptoms. A trial including 11 depressed patients demonstrated a significant reduction in anxiety symptoms (Hamilton Anxiety Rating Scale (HAM-A)) following ketamine infusion. This improvement is supported by one of the earlier placebo-controlled trials of ketamine which demonstrated that the psychic anxiety item was one of 4 (out of 21) items on the Hamilton Depression Rating Scale (HAM-D) demonstrating significant improvement after ketamine infusion.

The investigators goal is to conduct a randomized, placebo-controlled crossover study to explore the efficacy and time course of action of intravenous ketamine in the treatment of SAD.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Social Anxiety Disorder
Intervention  ICMJE
  • Drug: Ketamine
    Ketamine (a single 0.5mg/kg intravenously over 40 minutes).
  • Drug: Saline
    Saline (a single 0.5mg/kg intravenously over 40 minutes).
Study Arms  ICMJE
  • Experimental: Ketamine
    Ketamine will be given at a dose of 0.5mg/kg over 40 minutes. This dose is identical to that used in previous anti-depressant studies of Ketamine.
    Intervention: Drug: Ketamine
  • Placebo Comparator: Saline
    Saline will be given at a dose of 0.5 mg/kg over a 40 minute period.
    Intervention: Drug: Saline
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: March 7, 2014)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2018
Estimated Primary Completion Date March 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

Exclusion Criteria:

  1. Positive pregnancy test
  2. History of substance abuse disorder within the last 6 months or positive urine toxicology on screening (within the previous 6 months).
  3. History of pervasive developmental disorder or psychotic disorder by DSM-IV-TR criteria
  4. Medical comorbidity that significantly increases the risks associated with ketamine infusion (e.g. untreated hypertension, significant cardiovascular disease)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02083926
Other Study ID Numbers  ICMJE 1310012947
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Patterson Trust Awards Program in Clinical Research
Investigators  ICMJE
Principal Investigator: Michael H. Bloch, MD, MS Yale University
PRS Account Yale University
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP