Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ketamine Infusion for Social Anxiety Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

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.


Condition or disease Intervention/treatment Phase
Social Anxiety Disorder Drug: Ketamine Drug: Saline Early Phase 1

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ketamine Infusion for Social Anxiety Disorder
Study Start Date : March 2014
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : March 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety
Drug Information available for: Ketamine

Arm Intervention/treatment
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.
Drug: Ketamine
Ketamine (a single 0.5mg/kg intravenously over 40 minutes).

Placebo Comparator: Saline
Saline will be given at a dose of 0.5 mg/kg over a 40 minute period.
Drug: Saline
Saline (a single 0.5mg/kg intravenously over 40 minutes).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

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): NCT02083926


Locations
Layout table for location information
United States, Connecticut
Connecticut Mental Health Center
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
Patterson Trust Awards Program in Clinical Research
Investigators
Layout table for investigator information
Principal Investigator: Michael H. Bloch, MD, MS Yale University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02083926     History of Changes
Other Study ID Numbers: 1310012947
First Posted: March 11, 2014    Key Record Dates
Last Update Posted: July 12, 2016
Last Verified: July 2016
Keywords provided by Yale University:
Social Anxiety Disorder
SAD
Ketamine
Additional relevant MeSH terms:
Layout table for MeSH terms
Disease
Anxiety Disorders
Phobia, Social
Pathologic Processes
Mental Disorders
Phobic Disorders
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action