Ketamine in OCD: Efficacy and Effects on Stress and Cognition (KET-OCD)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Obsessive-Compulsive Disorder; Psychiatric Disorder
• Intervention / Treatment: Drug: Midazolam; Drug: Ketamine 50 MG/ML Blinded; Drug: Ketamine 50 MG/ML Open Label; Other: Treatment as Usual (TAU)

Detailed Description

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. Also EEG measurements will take place during and before infusions in this phase. Study subjects will be given an option to participate in an open-label follow up with up to 8 infusions over a period of a month. Open-label ketamine treatment will be compared to treatment as usual. After finishing open label treatment an additional EEG measurement will take place.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christoph Kraus, MD PhD; Phone Number: +4314040035680; Email: christoph.kraus@muv.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna, Department of Psychiatry and Psychotherapy
    • Contact: Christoph Kraus, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Experimental Group:

• 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

Exclusion Criteria Treatment as Usual Group:

• 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
• Any current severe personality disorder except comorbid anankastic personality disorder
• Current and unstable suicidality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ketamine; 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 Blinded; See also Arm description; Other Names: Randomized Controlled Phase Intervention 1; Drug: Ketamine 50 MG/ML Open Label; Open Label Follow Up (up to 8 Infusions); Other Names: Continuation Phase Intervention 1
Placebo Comparator: Midazolam; 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; See also Arm description; Other Names: Randomized Controlled Phase Intervention 2
Active Comparator: Treatment as Usual; Participants will receive standard-of-care treatment-which may include psychotherapy, pharmacotherapy, physiotherapy, ergotherapy, or a combination of these-at the discretion of the treating physician, independently of the study.	Other: Treatment as Usual (TAU); Treatment as Usual may include psychotherapy, pharmacotherapy, physiotherapy, ergotherapy, or a combination of these-at the discretion of the treating physician, independently of the study.; Other Names: Continuation Phase Intervention 2

What is the study measuring?

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 the Yale-Brown Obsessive Compulsive Scale (Y-BOCS; score range 0-40, with higher scores indicating greater severity).	In total 7 YBOCS assessments will take place between week 1 and 5.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 (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
Change of OCD symptoms (OCD-VAS)	There will be a change in patients' severity of obsessive and compulsive symptoms as measured with the Obsessive-Compulsive Disorder Visual Analog Scale (OCD-VAS; score range 0-600, with higher scores indicating greater severity) 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 the Yale-Brown Obsessive Compulsive Scale (Y-BOCS; score range 0-40, with higher scores indicating greater severity) 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 the Obsessive-Compulsive Disorder Visual Analog Scale (OCD-VAS; score range 0-600, with higher scores indicating greater severity) area under the curves.	in each arm 1 week after the infusion
Change of vegetative stress response (heart rate)	There will be a change of vegetative stress response 24 hours after ketamine infusion compared to midazolam infusion as measured by heart rate.	in each arm 24 hours after infusion
Change of vegetative stress response (blood pressure)	There will be a change of vegetative stress response 24 hours after ketamine infusion compared to midazolam infusion as measured by blood pressure.	in each arm 24 hours after infusion
Change in OCD symptoms (OCD-VAS)	Difference of the Obsessive-Compulsive Disorder Visual Analog Scale (OCD-VAS; score range 0-600, with higher scores indicating greater severity) scores a month after open-label treatment compared to treatment as usual, tested in a per protocol set.	One month after start of open-label treatment
Change in OCD symptoms (YBOCS)	Difference of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS; score range 0-40, with higher scores indicating greater severity) scores a month after open-label treatment compared to treatment as usual, tested in a per protocol set.	One month after start of open-label treatment
Changes in EEG frequency bands	There will be distinct changes in EEG frequency bands during ketamine infusion compared to midazolam. EEG will be recorded using a standard 32-channel montage. The following frequency bands will be analyzed at each channel: Delta (0.5-4 Hz), Theta (4-8 Hz), Alpha (8-13 Hz), Beta (13-30 Hz), and Gamma (>30 Hz).	EEG measurements will take place before (5 minutes resting state EEG) and during both infusions of the blinded phase as well as after the open label phase (10 minutes resting state and 5 minutes vigilance EEG).

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Christoph Kraus, MD PhD, Medical University of Vienna, Department of Psychiatry and Psychotherapy

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: September 25, 2022
• First Submitted That Met QC Criteria: October 10, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Ketamine; stress testing
• Additional Relevant MeSH Terms: Behavioral Symptoms; Personality Disorders; Anxiety Disorders; Problem Behavior; Mental Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics; Neurotransmitter Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Excitatory Amino Acid Agents; Anesthetics, Dissociative; Excitatory Amino Acid Antagonists; Midazolam; Ketamine
• Other Study ID Numbers: v6 05.05.2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No