Examining Mu Opioid Mechanisms of Ketamine's Rapid Effects in OCD (MKET2)

Study Overview
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Brief Summary
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The purpose of this study is to understand how ketamine works in the brain to bring about a reduction in OCD symptoms.

Detailed Description
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The proposed mechanistic trial would be the first to probe the role of ketamine's opioid properties in modulating fronto-striatal circuitry and bringing about reduction of OCD symptoms.

Official Title
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Examining Mu Opioid Mechanisms of Ketamine's Rapid Effects in OCD (MKET2)

Conditions
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Obsessive-Compulsive Disorder

Intervention / Treatment
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* Drug: Ketamine
* Drug: Naltrexone Pill
* Other: Placebo pill


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria for Participants with OCD: Inclusion Criteria: Ages 18-65 Meet the criteria for OCD diagnosis Failed at least 1 prior trial of standard first-line OCD treatment Agree to the following lifestyle modifications: comply with requirements for fasting prior to the Experimental Session, not enroll in any other interventional clinical trials during the duration of the study, and commit to medication study procedures. Able to provide informed consent Exclusion Criteria: prior naltrexone or ketamine use/exposure Any current or past medical/psychiatric condition that makes participation unsafe in the opinion of the investigator or study physician Pregnant or nursing, or able to become pregnant and are not practicing an effective means of birth control the presence of metal in the body that is contraindicated for MRI scans Eligibility Criteria for Healthy Volunteers: Inclusion Criteria: Ages 18-65 Able to provide informed consent Exclusion Criteria: current or past use of psychotropic medication pregnant or nursing females the presence of metal in the body that is contraindicated for MRI scans

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized with a 1:1 allocation to either IV ketamine + oral placebo or IV ketamine + oral opioid antagonist naltrexone
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine + Naltrexone<br>OCD patients in this arm will receive 0.5mg/kg of ketamine - one single infusion. fMRI will be acquired before, during, and after infusion. Oral naltrexone 50 mg will be administered before the infusion. | Drug: Ketamine<br>* Ketamine is an FDA-approved dissociative anesthetic.<br>* Other names: Ketalar;Drug: Naltrexone Pill<br>* Naltrexone is an oral opioid antagonist approved by the Food and Drug Administration (FDA) to treat both alcohol use disorder (AUD) and opioid use disorder (OUD)<br>* Other names: Naltrexone;|
| Placebo Comparator: Ketamine + Placebo<br>OCD patients in this arm will receive 0.5mg/kg of ketamine - one single infusion. fMRI will be acquired before, during, and after infusion. An oral inactive placebo will be administered before the infusion. | Drug: Ketamine<br>* Ketamine is an FDA-approved dissociative anesthetic.<br>* Other names: Ketalar;Other: Placebo pill<br>* An oral inactive placebo pill will be administered to preserve the blinded nature of the study.<br>|
| No Intervention: Healthy Volunteers<br>Healthy volunteers will have one fMRI scan visit. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the severity of OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS) | Change in OCD severity is measured by the YBOCS (Yale Brown Obsessive-Compulsive Scale), a gold standard measure of obsessions and compulsions. For the YBOCS the minimum units are 0 and Maximum units on the total scale are 40. The higher the number on the YBOCS, the more severe the symptoms. Response is defined as at least a 35% reduction on the YBOCS. | Baseline (Visit 2) to Post Infusion fMRI scan (Visit 4; Day 1), up to 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain Imaging, OCD symptoms, Obsessive-Compulsive Disorder, OCD, Ketamine, Naltrexone, MRI