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

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

Study Overview

• Status: Recruiting
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Drug: Ketamine; Drug: Naltrexone Pill; Other: Placebo pill

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pavithra Mukunda, MS; Phone Number: 6504972578; Email: ocdresearch@stanford.edu
• Study Contact Backup: Name: Carolyn I Rodriguez, MD, PhD; Phone Number: (650) 723-6158; Email: ocdresearch@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • Department of Psychiatry & Behavioral Sciences
      • Contact: OCD Research; Phone Number: 650-723-4095

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine + Naltrexone; 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; Ketamine is an FDA-approved dissociative anesthetic.; Other Names: Ketalar; Ketamine Hydrochloride; Drug: Naltrexone Pill; 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); Other Names: Naltrexone
Placebo Comparator: Ketamine + Placebo; 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; Ketamine is an FDA-approved dissociative anesthetic.; Other Names: Ketalar; Ketamine Hydrochloride; Other: Placebo pill; An oral inactive placebo pill will be administered to preserve the blinded nature of the study.
No Intervention: Healthy Volunteers; Healthy volunteers will have one fMRI scan visit.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Mental Health (NIMH)

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: July 3, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: MRI; OCD; Ketamine; Naltrexone; Brain Imaging; Obsessive-Compulsive Disorder; OCD symptoms
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Obsessive-Compulsive Disorder; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Naloxone; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Ketamine; Naltrexone
• Other Study ID Numbers: 70954; 1R01MH133553-01 (U.S. NIH Grant/Contract)

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