Intravenous Ketamine in the Treatment of Obsessive-Compulsive Disorder

NCT01371110 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: GCO 11-1113HSM#11-01536
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Obsessive Compulsive Disorder

Keywords

OCD; Obsessive-Compulsive Disorder; ketamine; treatment

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Percentage of Patients Who Meet Response and Remission

  up to 14 days

Study Arms (2)

Ketamine

ACTIVE COMPARATOR

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

Drug: Ketamine

Midazolam

SHAM COMPARATOR

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

Drug: Midazolam

Interventions

Ketamine 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.

Also known as: ketamine hydrochloride

Ketamine

Midazolam DRUG

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

Midazolam

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Wayne Goodman MD: lead
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (1)

Clinical Research Centers at Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Early termination due to limited funding lead to small numbers of subjects analyzed (n=3) compared to what was planned (n=12).

Results Point of Contact

• Title: Wayne Goodman
• Organization: Baylor College of Medicine (previously Icahn School of Medicine at Mount Sinai)

wayne.goodman@bcm.edu

713-798-4945

Study Officials

• 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)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor & Chair Psychiatry

Study Record Dates

• First Submitted: June 7, 2011
• First Posted: June 10, 2011
• Study Start: June 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: January 18, 2018
• Results First Posted: October 2, 2017

Record last verified: 2018-01

Locations

US (1)