Intravenous Ketamine in the Treatment of Obsessive-Compulsive Disorder (IVKetamine)

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.

Study Overview

• Status: Terminated
• Conditions: Obsessive Compulsive Disorder
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Clinical Research Centers at Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCCS) Rating OCD Symptom Severity From Baseline to 24-hours After Ketamine Administration	The primary efficacy outcome is change in the Y-BOCCS rating score on a scale from baseline to 24 hrs post-administration of ketamine. The 10 Y-BOCCS items are each scored on a four-point scale from 0 = "no symptoms" to 4 = "extreme symptoms." The sum of the first five items is a severity index for obsessions. The sum of the last five an index for compulsions. A translation of total score into an approximate index of overall severity is: 0-7 - subclinical; 8-15 - mild; 16-23 - moderate; 24-31 - severe; 32-40 - extreme.	Baseline and 24 Hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Meet Response and Remission	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.	up to 14 days

Collaborators and Investigators

• Sponsor: Wayne Goodman MD
• Collaborators: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Wayne K Goodman, MD, Baylor College of Medicine (previously Icahn School of Medicine at Mount Sinai); Principal Investigator: Kyle Lapidus, MD, (previously Icahn School of Medicine at Mount Sinai)

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): June 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: June 7, 2011
• First Submitted That Met QC Criteria: June 9, 2011
• First Posted (ESTIMATE): June 10, 2011

Study Record Updates

• Last Update Posted (ACTUAL): January 18, 2018
• Last Update Submitted That Met QC Criteria: January 16, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: treatment; OCD; ketamine; Obsessive-Compulsive Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Personality Disorders; Anxiety Disorders; Disease; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: GCO 11-1113; HSM#11-01536 (OTHER: THE MOUNT SINAI HEALTH SYSTEM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No