Intravenous Ketamine in the Treatment of Obsessive-Compulsive Disorder

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Mount Sinai School of Medicine
Sponsor:
Information provided by (Responsible Party):
Wayne Goodman, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01371110
First received: June 7, 2011
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

Obsessive-Compulsive Disorder (OCD) is a chronic and disabling anxiety disorder and a leading cause of worldwide disability that presents a significant public health problem. Treatment options are limited and many OCD patients fail to respond completely or quickly to standard treatments, including pharmacotherapy and psychotherapy. At this time, patients who fail to respond to treatment with serotonergic drugs, augmenting antipsychotic agents, and behavioral therapy, have few additional treatment options aside from deep brain stimulation. Therefore, despite advances in current pharmacological and behavioral treatments, and the utility of serotonergic drugs, it is likely that other neurotransmitter systems are involved and that targeting these systems may increase treatment efficacy. Despite little evidence for serotonergic dysfunction in OCD, there is significant evidence that glutamatergic dysregulation may contribute to the development and progression of the disorder. Also, preliminary studies suggest that glutamatergic modulators (i.e. riluzole and d-cycloserine), particularly agents acting at the NMDA receptor (i.e. memantine), may be useful in OCD. The NMDA antagonist, ketamine, has demonstrated rapid effects when delivered as a single intravenous (IV) dose in depressed patients. Therefore, the objective of the current study is to investigate the safety and efficacy of a single dose of IV ketamine in treatment-resistant OCD.


Condition Intervention Phase
Obsessive Compulsive Disorder
Drug: Ketamine
Drug: Midazolam
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Intravenous Ketamine in the Treatment of Obsessive-Compulsive Disorder

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Change in Y-BOCCS from baseline to 24-hours after ketamine administration [ Time Frame: Baseline and 24 Hours ] [ Designated as safety issue: No ]
    The primary efficacy outcome is change in the Y-BOCCS from baseline to 24 hrs post-administration of ketamine.


Secondary Outcome Measures:
  • Percentage of patients who meet response and remission [ Time Frame: up to 14 days ] [ Designated as safety issue: No ]
    Percentage of patients who meet response (defined as 25% reduction in Y-BOCCS score) and remission (defined as Y-BOCS score ≤10) criteria at 24 hrs post-infusion and durability of efficacy up to two weeks after administration. Assessments will be performed 24, 48 and 72 hrs post-infusion and after 7, 10, and 14 days.


Estimated Enrollment: 12
Study Start Date: June 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ketamine
Study participants will receive a one-time intravenous infusion of 0.5 mg/kg racemic ketamine hydrochloride
Drug: Ketamine
Ketamine hydrochloride is a nonbarbiturate anesthetic. It is formulated as a slight acid (pH 3.5 to 5.5) sterile solution for intravenous or intramuscular injection in concentrations containing the equivalent of either 50 or 100mg ketamine base per milliliter.
Other Name: ketamine hydrochloride
Sham Comparator: Midazolam
Study participants will receive a one-time intravenous infusion of 0.045 mg/kg midazolam
Drug: Midazolam
Midazolam is a short-acting benzodiazepine central nervous (CNS) depressant.

Detailed Description:

This study will test the safety and efficacy of a single intravenous (IV) dose of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, ketamine, in treatment-resistant OCD.

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients, 21-65 years
  • Women of childbearing potential must agree to use a medically accepted means of contraception for the duration of the study
  • Primary diagnosis of Obsessive-Compulsive Disorder as assessed by the SCID-P, with symptoms for at least 1 year (Patients who meet criteria for OCD will be required to be medication free or have all psychotropics aside from SSRIs and as needed benzodiazepines tapered. Prior to study entry, proscribed psychotropics are tapered, and subjects must be on the same SSRI for at least 8 weeks with no change in dose for at least 4 weeks and throughout the study. However, subjects will be allowed to use benzodiazepines as needed throughout the study.)
  • History of a failure to respond to at least two (2) adequate pharmacotherapy trials and CBT for OCD
  • Subjects must have scored ≥ 21 on the Y-BOCS at Screening, and to not be in remission on Treatment Day #1, and Treatment Day #2
  • Each subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document
  • Subjects must be able to identify a family member, physician, or friend who will participate in the Treatment Contract and serve as an emergency contact.

Exclusion Criteria:

  • Women who plan to become pregnant within the next six months, are pregnant or are breast-feeding
  • Non-English speakers
  • Any unstable medical illness including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease
  • Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG
  • Lifetime history of schizophrenia, schizoaffective disorder, bipolar disorder, mental retardation, or pervasive developmental disorders
  • Current evidence of psychotic or manic symptoms
  • Drug or alcohol abuse or dependence within the preceding 6 months
  • Lifetime abuse or dependence on ketamine or phencyclidine
  • Patients judged by study investigator to be at high risk for suicide
  • Current use of psychotropics other than SSRIs
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01371110

Contacts
Contact: Wayne K Goodman, MD 212-659-8860 wayne.goodman@mssm.edu
Contact: Kyle Lapidus, MD 212-659-8804 kyle.lapidus@mssm.edu

Locations
United States, New York
Clinical Research Centers at Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Principal Investigator: Wayne K Goodman, MD         
Principal Investigator: Kyle Lapidus, MD         
Sponsors and Collaborators
Wayne Goodman
Investigators
Principal Investigator: Wayne K Goodman, MD Mount Sinai School of Medicine
Principal Investigator: Kyle Lapidus, MD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Wayne Goodman, Professor & Chair Psychiatry, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01371110     History of Changes
Other Study ID Numbers: GCO 11-1113, HSM#11-01536
Study First Received: June 7, 2011
Last Updated: March 26, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:
OCD
Obsessive-Compulsive Disorder
ketamine
treatment

Additional relevant MeSH terms:
Obsessive-Compulsive Disorder
Compulsive Personality Disorder
Anxiety Disorders
Mental Disorders
Personality Disorders
Ketamine
Midazolam
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Hypnotics and Sedatives
GABA Modulators
GABA Agents

ClinicalTrials.gov processed this record on July 22, 2014