Ketamine and Stress in OCD

Study Overview
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Brief Summary
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The main goal of this trial is to demonstrate therapeutic efficacy of low dose ketamine in patients with OCD. We expect that ketamine will alleviate symptoms in the hours following application, but also - if effective - that the anti-OCD effects might last for several days after a single infusion.

Detailed Description
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This study will apply a randomized, double blind, comparator-controlled cross-over design and will be conducted at the Department of Psychiatry and Psychotherapy of the Medical University of Vienna. We will include 30 participants with a primary diagnosis of OCD. Participants will undergo ketamine and comparator infusions in either inpatient- or outpatient settings to assess the therapeutic capabilities of ketamine in OCD. Furthermore, participants' neurocognitive function and stress responses will be tested with four neurocognitive tasks and a cold pressor test paradigm.

Official Title
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Ketamine Therapy in Obsessive-compulsive Disorder and Its Effects on Neuropsychological Function Under Stress in a Cross-over Trial

Conditions
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Obsessive-Compulsive Disorder, Psychiatric Disorder

Intervention / Treatment
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* Drug: Ketamine 50 MG/ML
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary diagnosis of obsessive-compulsive disorder A score of 16 or higher on the Yale-Brown Obsessive Compulsive Scale and ability to provide written informed consent At least one previous treatment for OCD Exclusion Criteria: Any history of current or past psychotic disorder A manic episode within the preceding three years Current or unstable remitted substance abuse or dependence except nicotine Pregnancy or elevated risk of becoming pregnant during study duration (desire to have children) and refusal to utilize a proper method of contraception Any current severe personality disorder except comorbid anankastic personality disorder Morbus Raynaud Inability to follow the study protocol or adhere to operational requirements Current and unstable suicidality Unstable hypertension Untreated hyperthyroidism Any unstable cardiovascular disease Untreated disorders severely affecting the HPA-axis (M.Addison, M.Cushing) Current pharmacological therapy severely affecting the HPA-axis like corticosteroids or ACTH

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study will apply a randomized, double blind, comparator-controlled cross-over design. The order of treatment modality will be randomized and double-blind. Participants will undergo one infusion of ketamine and midazolam as comparator. They will be assigned to one of two sequenced treatment groups, with one group first receiving verum and after 14 days the comparator infusion, the other group vice versa. The randomization into these two sequence groups will be stratified for symptom severity, defined as moderate (YBOCS baseline >16) or severe (YBOCS baseline >25).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ketamine<br>Participants will undergo one infusion of ketamine as active comparator. (R,S-ketamine 50mg/ml solution for injection, dose: 0,5 mg per kg bodyweight) Both medications will be diluted in 100 ml saline and will be adjusted for infusion over 40 minutes, administered with a syringe pump. | Drug: Ketamine 50 MG/ML<br>* See also Arm description<br>|
| Placebo Comparator: Midazolam<br>Participants will undergo one infusion of midazolam as comparator. (0,045 mg/kg bodyweight) Both medications will be diluted in 100 ml saline and will be adjusted for infusion over 40 minutes, administered with a syringe pump. | Drug: Midazolam<br>* See also Arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of OCD symptoms (Y-BOCS) | There will be a change of severity of obsessive and compulsive symptoms seven days after ketamine infusion compared to midazolam infusion as measured with Y-BOCS. | In total 7 YBOCS assessments will take place between week 1 and 5. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of OCD symptoms (OCD-VAS) | There will be a change in patients' severity of obsessive and compulsive symptoms as measured with OCD-VAS 24 hours after ketamine infusion compared to midazolam infusion. | in each arm 24 hours after infusion | 
| Change of OCD symptoms (Y-BOCS) | There will be a change in patients' severity of obsessive and compulsive symptoms as measured with YBOCS 24 hours after ketamine infusion compared to midazolam infusion. | in each arm 24 hours after infusion | 
| Change of OCD symptoms (OCD-VAS) | There will be a change of symptoms over the course of seven days after ketamine infusion compared to midazolam infusion as measured with OCD-VAS area under the curves. | in each arm 1 week after the infusion | 
| Change in neuropsychological function | There will be a change in neuropsychological function after 24 hours after ketamine infusion compared to midazolam infusion as measured by four neurocognitive tests (N-Back, WCST, SSRT, ToH) | in each arm 24 hours after infusion | 
| Change in cortisol response | There will be a change in cortisol response to stress 24 hours after ketamine infusion compared to midazolam infusion. | in each arm 24 hours after infusion | 
| Change of vegetative stress response (cardiovascular) | There will be a change of vegetative stress response 24 hours after ketamine infusion compared to midazolam infusion as measured with cardiovascular parameters (HR, BP). | in each arm 24 hours after infusion | 
| Change of vegetative stress response (stress VAS) | There will be a change of vegetative stress response 24 hours after ketamine infusion compared to midazolam infusion as measured with subjective stress VAS. | in each arm 24 hours after infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine, stress testing