Intravenous Ketamine in the Treatment of Obsessive-Compulsive Disorder
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.
Obsessive Compulsive Disorder
|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|
- 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.
- 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.
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||August 2013|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Ketamine
Study participants will receive a one-time intravenous infusion of 0.5 mg/kg racemic ketamine hydrochloride
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
Midazolam is a short-acting benzodiazepine central nervous (CNS) depressant.
Overview 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. The proposed research plan calls for the recruitment of 12 patients, aged 21-65, with Obsessive Compulsive Disorder. Study participants will have failed to respond to at least two (2) previous adequate pharmacotherapy trials. Participants will be continued on their prior medications and ketamine will be an adjunctive treatment. This unique "proof-of-concept" study in OCD will be conducted over a 1-year period at Mount Sinai School of Medicine (MSSM) using a randomized, double-blind, cross-over design. The clinical response to a single IV dose of ketamine (0.5mg/kg infused over 40 min) will be compared with the clinical response to a single IV dose of midazolam (0.045mg/kg infused over 40 min). The two administrations will be separated by two weeks and will be procedurally similar to previous IV ketamine studies at MSSM and other institutions in major depression; specifically, administration will take place in a controlled medical setting with close medical and psychiatric monitoring. Participants will be required to have at least moderate to severe OCD as indicated by a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of at least 21 within 24 hrs pre-infusion and to not be in remission (defined as Y-BOCS score ≤10) on each treatment day (Treatment Day #1 and #2). The primary efficacy outcome is change in the Y-BOCCS from baseline to 24 hrs post-administration. Secondary outcomes will include 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.
Details of Study Design Baseline: After receiving a complete description of the research and reviewing the informed consent form, potential participants will be given the opportunity to ask questions and sign the consent form if they so choose. All potential study participants will also be evaluated for capacity to consent by a psychiatrist who is independent from the study team. A study investigator will obtain additional medical and psychiatric history and history of response to previous treatments. The diagnosis of Obsessive-Compulsive Disorder will be made using the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-P). The Y-BOCS will be used at baseline to determine current severity of OCD symptoms. Patients who meet criteria for OCD will be required to be medication free or have all psychotropics aside from SSRIs 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. Subjects must have a Y-BOCS score ≥ 21 at the screening visit and not be in remission within 24-hrs of each of the two infusion days (Treatment Day #1 and #2) to be included in the study. Other instruments to be administered at screening will include the Yale-Brown Obsessive Compulsive Challenge Scale (Y-BOCCS), the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Psychiatric Rating Scale for Depression (HAM-D), the Hamilton Psychiatric Rating Scale for Anxiety (HAM-A), the Wechsler Abbreviated Scale of Intelligence-Subtest (WASI), the Hopkins Verbal Learning Test (HVLT) and the Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR16).
Eligible participants will meet treatment-resistant criteria if they have failed to respond to ≥ 2 adequate pharmacotherapy trials with SRIs that are FDA approved medications for OCD (SSRIs or clomipramine) with or without adjunctive antipsychotics, as well as cognitive behavioral therapy. All patients will have a physical examination, electrocardiogram (ECG), urine toxicology and routine laboratory blood tests. The medical screening will take place at the Mount Sinai General Clinical Research Center (GCRC). A pregnancy test will be performed in premenopausal women.
|Contact: Wayne K Goodman, MDfirstname.lastname@example.org|
|Contact: Kyle Lapidus, MDemail@example.com|
|United States, New York|
|Clinical Research Centers at Mount Sinai School of Medicine||Recruiting|
|New York, New York, United States, 10029|
|Principal Investigator: Wayne K Goodman, MD|
|Principal Investigator: Kyle Lapidus, MD|
|Principal Investigator:||Wayne K Goodman, MD||Mount Sinai School of Medicine|
|Principal Investigator:||Kyle Lapidus, MD||Mount Sinai School of Medicine|