A Trial of Intranasal Ketamine for the Treatment of Obsessive-Compulsive Disorder

Study Overview
=================
Brief Summary
-----------------
This study is being done to learn whether administration of intranasal (inhaled through the nose) ketamine reduces symptoms of obsessive-compulsive disorder (OCD). Ketamine has been approved by the U.S. Food and Drug Administration (FDA) as an anesthetic agent (a medicine to reduce pain during surgery and other procedures) but ketamine has not been approved by the FDA as a treatment for OCD. The investigators believe that ketamine may be effective in reducing symptoms of OCD due to its ability to decrease the activity of a specific brain chemical called glutamate. Previous studies have shown that people with OCD can have abnormal levels of glutamate in their brains. This is the first time that intranasal ketamine is being studied in people with OCD. However, studies have been done in the past using intravenous (IV; through a needle into a vein in your arm) ketamine in people with OCD, and intranasal ketamine has been studied in people with other psychiatric conditions. This research study will compare ketamine to placebo. The placebo looks exactly like ketamine, but contains no ketamine. At some time during the study, the investigators will give you ketamine. At another time, the investigators will give you placebo. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons.

Official Title
-----------------
A Placebo-Controlled Crossover Trial of Intranasal Ketamine for the Treatment of Obsessive-Compulsive Disorder

Conditions
-----------------
Obsessive-Compulsive Disorder

Intervention / Treatment
-----------------
* Drug: Ketamine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female age ≥ 18 and ≤ 55 Meets DSM-IV50 criteria for OCD as the primary presenting diagnosis as determined by the investigator (participants with secondary comorbid dysthymia, major depression, anxiety disorders, eating disorders, and other obsessive-compulsive spectrum disorders will still be eligible for enrollment). Score of ≥ 18 on the Y-BOCS at screening Exclusion Criteria: Unwillingness or inability to provide written informed consent. Active suicidal ideation at screening Lifetime history of psychotic disorder or autism spectrum disorder DSM-IV diagnosis of alcohol or substance dependence, with the exception of nicotine dependence, within three months prior to screening Any history of intolerance or hypersensitivity to ketamine Any history of nasal/sinus anomalies or dysfunction (e.g., nasal obstruction or history of nasal surgery) Clinically significant medical disease including, but not limited to, cardiac (including uncontrolled hypertension or uncontrolled hypotension, arrhythmias, congestive heart failure, angina), pulmonary, hepatic, renal, or endocrine disorders, which would increase the risk to the participant or interfere with interpretation of results as judged by the principal investigator. Clinically significant neurologic disease including, but not limited to, seizure disorder, neurodegenerative diseases, transient ischemic attacks, neural vascular disease, stroke, cerebral aneurysms, and history of traumatic brain injury. Female participants with a positive serum or urine pregnancy test at screening Pregnancy. Females of childbearing potential must be using an effective contraceptive method (e.g., abstinence, prescription oral contraceptives, contraceptive injections, double-barrier method, male partner sterilization). Women that are not of childbearing potential are defined as: postmenopausal (>45 years of age with amenorrhea for at least 12 months, or any age with menorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level >40 IU/ml); permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy. Female participants who are lactating. Any screening laboratory abnormality deemed clinically significant by the investigator Currently taking opiate pain medications, dextromethorphan, St. John's Wort, theophylline, or tramadol. Any participation in an investigational drug trial within 30 days of enrollment in study. Contraindication to having an MRI.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine/Placebo<br>Participants in this group will receive 5 sprays (10 mg each) of intranasal ketamine for the first treatment visit, then receive 5 sprays of placebo (saline solution) at the second treatment visit two weeks later. | Drug: Ketamine<br> <br> Drug: Placebo<br> <br> |
| Experimental: Placebo/Ketamine<br>Participants in this group will receive 5 sprays of placebo (saline solution) for the first treatment visit, then receive 5 sprays (10 mg each) of intranasal ketamine at the second treatment visit two weeks later. | Drug: Ketamine<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observing if Ketamine May Cause a Decrease in OCD Symptoms | Examining if ketamine is associated with a decrease in OCD symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at completion of one treatment when compared to placebo (saline solution). The Y-BOCS measures OCD symptoms on a scale of 0-40, with higher numbers indicating greater severity of OCD symptoms. For this study, subjects had to have a Y-BOCS of greater than or equal to 18 in order to participate. | Baseline to Week 5 |