An Early Phase 1 interventional study of Ketamine and Saline in Social Anxiety Disorder, sponsored by Yale University. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2021-03-18.
Sponsored by Yale University · Early Phase 1, Interventional, and Treatment
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.
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.
4,868 studies on the registry are indexed under Anxiety Disorders; 1,390 are open to participants now.
This study's enrollment of 18 is below the median of 80 across 4,174 interventional studies indexed under Anxiety Disorders.
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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
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
Ketamine (a single 0.5mg/kg intravenously over 40 minutes).
Also known as: Ketalar
Saline (a single 0.5mg/kg intravenously over 40 minutes).
Also known as: Placebo
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.
Time frame: 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
Time frame: Day 1 (1+28)
| Milestone | Ketamine Infusion on Day 0, Saline Infusion on Day 28 | Saline Infusion on Day 0, Ketamine Infusion on Day 28 |
|---|---|---|
| Started | 9 | 9 |
| Completed | 8 | 9 |
| Not completed | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
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.
| units on a scale | Ketamine Infusion on Day 0 or Day 28 | Saline Infusion on Day 0 or Day 28 |
|---|---|---|
| Visual Analogue Scale for Anxiety Symptoms (VAS-anxiety) | 12.1 ± 18.6 | 19.6 ± 18.5 |
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
| score on a scale | Ketamine Infusion on Day 0 or Day 28 | Saline Infusion on Day 0 or Day 28 |
|---|---|---|
| Liebowitz Social Anxiety Score (LSAS) | 66.1 ± 30.9 | 86.1 ± 30 |
Collected over 1 hour after infusion. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ketamine Infusion on Day 0 or Day 28 | 0/18 (0%) | 0/18 (0%) | 15/18 (83.3%) |
| Saline Infusion on Day 0 or Day 28 | 0/17 (0%) | 0/17 (0%) | 4/17 (23.5%) |
| Event | Ketamine Infusion on Day 0 or Day 28 | Saline Infusion on Day 0 or Day 28 |
|---|---|---|
| Spaced outNervous system disorders | 13/18 | 4/17 |
| things seem unrealNervous system disorders | 9/18 | 3/17 |
| parestesias and numbnessNervous system disorders | 9/18 | 0/17 |
| gaps in your memoryNervous system disorders | 8/18 | 0/17 |
| things seem to be movingNervous system disorders | 7/18 | 2/17 |
| Feel like a spectatorNervous system disorders | 7/18 | 2/17 |
| Things you can't account forNervous system disorders | 6/18 | 1/17 |
| dizzinessNervous system disorders | 6/18 | 0/17 |
| Feel disconnected from your own bodyNervous system disorders | 5/18 | 2/17 |
| Feel as if you were in a tunnelNervous system disorders | 5/18 | 1/17 |
| Age, Categorical(Participants) | Ketamine Infusion on Day 0, Saline Infusion on Day 28 | Saline Infusion on Day 0, Ketamine Infusion on Day 28 | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 9 | 9 | 18 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Ketamine Infusion on Day 0, Saline Infusion on Day 28 | Saline Infusion on Day 0, Ketamine Infusion on Day 28 | Total |
|---|---|---|---|
| Mean | 30.78 ± 13.50 | 28.67 ± 8.66 | 29.72 ± 11.05 |
| Sex: Female, Male(Participants) | Ketamine Infusion on Day 0, Saline Infusion on Day 28 | Saline Infusion on Day 0, Ketamine Infusion on Day 28 | Total |
|---|---|---|---|
| Female | 2 | 5 | 7 |
| Male | 7 | 4 | 11 |
| Race/Ethnicity, Customized(Participants) | Ketamine Infusion on Day 0, Saline Infusion on Day 28 | Saline Infusion on Day 0, Ketamine Infusion on Day 28 | Total |
|---|---|---|---|
| Non-Hispanic White | 8 | 6 | 14 |
| Non-Hispanic Asian | 0 | 2 | 2 |
| Hispanic | 1 | 1 | 2 |
| Region of Enrollment(participants) | Ketamine Infusion on Day 0, Saline Infusion on Day 28 | Saline Infusion on Day 0, Ketamine Infusion on Day 28 | Total |
|---|---|---|---|
| United States | 9 | 9 | 18 |
| Visual Analogue Scale for anxiety symptoms (VAS-anxiety)(units on a scale) | Ketamine Infusion on Day 0, Saline Infusion on Day 28 | Saline Infusion on Day 0, Ketamine Infusion on Day 28 | Total |
|---|---|---|---|
| Mean | 47.22 ± 18.89 | 57.78 ± 19.70 | 47.22 ± 18.89 |
| Liebowitz Social Anxiety Score (LSAS)(units on a scale) | Ketamine Infusion on Day 0, Saline Infusion on Day 28 | Saline Infusion on Day 0, Ketamine Infusion on Day 28 | Total |
|---|---|---|---|
| Mean | 93.89 ± 19.37 | 87.44 ± 14.53 | 90.67 ± 16.94 |
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Yale University