Intravenous Ketamine in the Treatment of Obsessive-Compulsive Disorder

NCT ID: NCT01371110

Last Updated: 2018-01-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2015-06-30

Brief Summary

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.

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.

Conditions

Obsessive Compulsive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ketamine

Study participants will receive a one-time intravenous infusion of 0.5 mg/kg racemic ketamine hydrochloride

Group Type: ACTIVE_COMPARATOR

Ketamine

Intervention Type: DRUG

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.

Midazolam

Study participants will receive a one-time intravenous infusion of 0.045 mg/kg midazolam

Group Type: SHAM_COMPARATOR

Midazolam

Intervention Type: DRUG

Midazolam is a short-acting benzodiazepine central nervous (CNS) depressant.

Interventions

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.

Intervention Type: DRUG

Midazolam

Midazolam is a short-acting benzodiazepine central nervous (CNS) depressant.

Intervention Type: DRUG

Other Intervention Names

ketamine hydrochloride

Eligibility 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

Wayne Goodman MD

OTHER

Sponsor Role: lead

Responsible Party

Wayne Goodman MD

Professor & Chair Psychiatry

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Wayne K Goodman, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine (previously Icahn School of Medicine at Mount Sinai)

Kyle Lapidus, MD

Role: PRINCIPAL_INVESTIGATOR

(previously Icahn School of Medicine at Mount Sinai)

Locations

Clinical Research Centers at Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

Other Identifiers

HSM#11-01536

Identifier Type: OTHER

Identifier Source: secondary_id

GCO 11-1113

Identifier Type: -

Identifier Source: org_study_id