Ketamine Infusion for Obsessive-Compulsive Disorder

Sponsor
Yale University (Other)
Overall Status
Completed
CT.gov ID
NCT01349231
Collaborator
National Alliance for Research on Schizophrenia and Depression (Other)
10
1
1
33.9
0.3

Study Details

Study Description

Brief Summary

Roughly one-third of patients with obsessive-compulsive disorder (OCD) do not experience significant clinical benefit from first-line interventions such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or cognitive behavioral therapy (CBT). Furthermore, OCD patients typically experience the full treatment benefits of first-line interventions only after a time-lag of two to three months. Inadequate symptom relief and delay of symptom relief from first-line treatments are sources of substantial morbidity and decreased quality of life in OCD patients. Converging lines of evidence from neuroimaging, genetic and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of OCD.

The investigators are conducting an open, uncontrolled study of ketamine in treatment-refractory OCD. Ketamine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor and has been demonstrated to have rapid anti-depressant effects in patients with Major Depressive Disorder. The investigators have additionally provided evidence for rapid improvement of comorbid OCD and trichotillomania after ketamine infusion in a depressed woman.

Failure of symptom relief and delay of symptom relief from first-line treatments are a source of substantial morbidity and decreased quality of life in OCD patients. Ketamine represents the possibility to provide rapid symptom relief to OCD patients and may provide the mechanism for future drug development to treat OCD more rapidly and effectively.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Roughly one-third of patients with obsessive-compulsive disorder (OCD) fail to experience significant clinical benefit from first-line interventions such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or cognitive behavioral therapy (CBT). Antipsychotic augmentation is the only pharmacological strategy for treatment-refractory OCD with demonstrated efficacy in multiple double-blind trials (2). Antipsychotic augmentation only benefits around 1 in 3 treatment-refractory OCD. Furthermore, OCD patients typically experience the full treatment benefits of first-line interventions only after a time-lag of two to three months. Failure of symptom relief and delay of symptom relief from first-line treatments are sources of substantial morbidity and decreased quality of life in OCD patients.

Converging lines of evidence from neuroimaging, genetic and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of OCD. In Magnetic Resonance Spectroscopy studies elevated concentrations of glutamate and related compounds have been demonstrated in the caudate nucleus and orbitofrontal cortex of OCD patients compared to normal controls. In genetic studies, single nucleotide polymorphisms within the glutamate transporter gene SLC1A1 have been associated with the diagnosis of OCD. Open-label, pharmacological treatment studies have suggested that glutamate modulating agents such as riluzole, n-acetylcysteine and memantine may be effective in the treatment of OCD.

Ketamine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor, a major type of glutamate receptor in the brain. In a placebo-controlled study completed at Yale a single dose of ketamine (0.5 mg/kg, intravenously) had rapid antidepressant effects in depressed patients. In these subjects ketamine infusion produced mild psychotomimetic symptoms and euphoria that dissipated within 120 minutes, while the antidepressant effects of ketamine infusion emerged over the first 180 minutes and persisted over 72 hours. Fifty percent of depressed patients receiving ketamine were treatment responders at Day 3 compared to 12.5% in the placebo infusion group. These results have been replicated in a recent double-blind study performed at NIMH and a third unpublished study conducted by members of our group at Yale.

Our goal is to conduct an open-label study in treatment-refractory OCD to determine if ketamine may be an effective acute anti-obsessional agent.

Study Design

Study Type:
Interventional
Actual Enrollment :
10 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Ketamine Infusion for Obsessive-Compulsive Disorder
Study Start Date :
Feb 1, 2009
Actual Primary Completion Date :
Dec 1, 2011
Actual Study Completion Date :
Dec 1, 2011

Arms and Interventions

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 intravenously over 40 minutes).

Outcome Measures

Primary Outcome Measures

  1. OCD Severity [Baseline and 1 day after ketamine infusion]

    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 1 day following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.

  2. OCD Severity [Baseline and 2 days following infusion]

    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 2 days following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.

  3. OCD Severity [Baseline and 3 days following infusion]

    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 3 days following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.

Secondary Outcome Measures

  1. Depression Symptoms [Baseline, Day 1, Day 2, and Day 3]

    We will examine change from baseline in Hamilton Rating Scale for Depression (HRDS) ratings of depression severity at day 1-3 following a single ketamine infusion. The HRDS assesses severity of, and change in, depressive symptoms. The HRDS is a 21 item scale with scores ranging from 0-66. The higher the score, the more severe the depression.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Adult between the ages of 18 and 65 years.

  2. Meet DSM IV criteria for obsessive-compulsive disorder by structured clinical interview (SCID) and have a Y-BOCS score >24.

  3. Have treatment-refractory OCD. Have Y-BOCS>24 despite two SSRI trials of adequate dose and duration and been offered prior CBT treatment.

  4. Stable psychiatric medications. Subjects must have had stable doses of all psychiatric medications for the month prior to treatment and have been on stable doses of SSRI and clomipramine for at least 2 months prior to study enrollment.

  5. Medically and neurologically healthy.

  6. Able to provide written informed consent according to the Yale HIC guidelines.

Exclusion Criteria:
  1. Lifetime history of substance dependence (other than nicotine and caffeine)

  2. Suicide attempt or suicidal ideation requiring psychiatric hospitalization in the previous 6 months

  3. Being Pregnant

  4. Known hypersensitivity to ketamine

Contacts and Locations

Locations

Site City State Country Postal Code
1 Connecticut Mental Health Center/ YNHH New Haven Connecticut United States 06520

Sponsors and Collaborators

  • Yale University
  • National Alliance for Research on Schizophrenia and Depression

Investigators

  • Principal Investigator: Michael H Bloch, MD, MS, Yale University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Yale University
ClinicalTrials.gov Identifier:
NCT01349231
Other Study ID Numbers:
  • 0901004660
First Posted:
May 6, 2011
Last Update Posted:
Jun 9, 2014
Last Verified:
May 1, 2014

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Ketamine
Arm/Group Description 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. ketamine: Ketamine (a single 0.5mg intravenously over 40 minutes).
Period Title: Overall Study
STARTED 10
COMPLETED 10
NOT COMPLETED 0

Baseline Characteristics

Arm/Group Title Ketamine
Arm/Group Description 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. ketamine: Ketamine (a single 0.5mg intravenously over 40 minutes).
Overall Participants 10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
41.7
(13.5)
Age (Count of Participants)
<=18 years
0
0%
Between 18 and 65 years
10
100%
>=65 years
0
0%
Sex: Female, Male (Count of Participants)
Female
4
40%
Male
6
60%
Region of Enrollment (participants) [Number]
United States
10
100%
Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]
32.9
(1.9)

Outcome Measures

1. Primary Outcome
Title OCD Severity
Description We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 1 day following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.
Time Frame Baseline and 1 day after ketamine infusion

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine
Arm/Group Description 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. ketamine: Ketamine (a single 0.5mg intravenously over 40 minutes).
Measure Participants 10
Mean (Standard Deviation) [units on a scale]
-2.7
(1.11)
2. Primary Outcome
Title OCD Severity
Description We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 2 days following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.
Time Frame Baseline and 2 days following infusion

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine
Arm/Group Description 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. ketamine: Ketamine (a single 0.5mg intravenously over 40 minutes).
Measure Participants 10
Mean (Standard Deviation) [units on a scale]
-3.6
(1.19)
3. Primary Outcome
Title OCD Severity
Description We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 3 days following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.
Time Frame Baseline and 3 days following infusion

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine
Arm/Group Description 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. ketamine: Ketamine (a single 0.5mg intravenously over 40 minutes).
Measure Participants 10
Mean (Standard Deviation) [units on a scale]
-2.9
(0.91)
4. Secondary Outcome
Title Depression Symptoms
Description We will examine change from baseline in Hamilton Rating Scale for Depression (HRDS) ratings of depression severity at day 1-3 following a single ketamine infusion. The HRDS assesses severity of, and change in, depressive symptoms. The HRDS is a 21 item scale with scores ranging from 0-66. The higher the score, the more severe the depression.
Time Frame Baseline, Day 1, Day 2, and Day 3

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Ketamine
Arm/Group Description 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. ketamine: Ketamine (a single 0.5mg intravenously over 40 minutes).
Measure Participants 10
HRDS change from Baseline to Day 1
-6.57
(1.69)
HRDS change from Baseline to Day 2
-7.29
(2.89)
HRDS change from Baseline to Day 3
-5.14
(2.48)

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group Title Ketamine
Arm/Group Description 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. ketamine: Ketamine (a single 0.5mg intravenously over 40 minutes).
All Cause Mortality
Ketamine
Affected / at Risk (%) # Events
Total / (NaN)
Serious Adverse Events
Ketamine
Affected / at Risk (%) # Events
Total 0/10 (0%)
Other (Not Including Serious) Adverse Events
Ketamine
Affected / at Risk (%) # Events
Total 5/10 (50%)
General disorders
Transient increase in systolic blood pressure 1/10 (10%)
Psychiatric disorders
Dysphoria 2/10 (20%)
Dissociative symptoms 5/10 (50%)
Anxiety 2/10 (20%)
Passive suicidal ideation 2/10 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dr. Michael Bloch, MD, MS
Organization Yale University, Connecticut Mental Health Center
Phone 203-737-4809
Email michael.bloch@yale.edu
Responsible Party:
Yale University
ClinicalTrials.gov Identifier:
NCT01349231
Other Study ID Numbers:
  • 0901004660
First Posted:
May 6, 2011
Last Update Posted:
Jun 9, 2014
Last Verified:
May 1, 2014