Imaging Neural Correlates of Ketamine Using PET/MR (RSKet)

Imaging Neural Correlates of Antidepressant Action of Ketamine Stereoisomers Using Pharmacological PET/MR Imaging and Metabolite Analysis.

The purpose of this randomized, placebo-controlled study is to investigate pharmacodynamic differences between racemic ketamine and esketamine using functional fluorodeoxyglucose ([18F]FDG) positron emission tomography/magnetic resonance imaging (PET/MR)

Pilot study I:

A pilot study with healthy controls will be performed in order to investigate pharmacokinetic behavior and acute behavioral effects of intravenous ketamine infusion.

Pilot study II:

A pilot study including 15 healthy volunteers will be performed in order to optimize scanning procedures. The pilot study follows a randomized, placebo-controlled, double-blind, cross-over study design. After enrollment into the study all subjects will undergo two [18F]FDG PET/CT scans in the course of which they will receive either S-ketamine or placebo during the first scan and the respective other study medication during the second scan.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Ketamine Hydrochloride; Drug: Esketamine; Drug: Pilot study II: Esketamine; Drug: Pilot study II: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Rupert Lanzenberger, Prof.; Phone Number: 004314040035760; Email: rupert.lanzenberger@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Rupert Lanzenberger, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• General health based on medical history, physical examination and structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (SCID)
• Age 18 to 55 years
• Right-handedness (due to potential lateralization effects of lefthanded subjects)
• Willingness and competence to sign the informed consent form.

Exclusion Criteria:

• Current or history of psychiatric or neurological disease
• Current medical illness requiring treatment
• Pregnancy or current breastfeeding
• Current or former substance abuse
• Diagnosis of an Axis-1 psychotic disorder in a first-degree relative
• Any contraindication for MRI (e.g., MR incompatible implants, etc.) including dental implants causing signal artifacts
• For subjects participating in earlier studies using ionizing radiation, the total radiation exposure of 30 millisievert (mSv) over the last 10 years must not be exceeded, as specified in the Austrian legislation on radiation protection (www.ris.bka.gv.at). Accordingly, body weight >100kg is an exclusion criterion (5.1 Megabequerel (MBq)/kg * 100kg * 0.019 mSv/MBq* 0.885 = 8.58 mSv per scan, the factor 0.885 is considered due to continuous radioligand infusion, see PET scanning).
• Failure to comply with the study protocol or to follow the instruction of the investigating team.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esketamine ((S)-Ketamine); Single-blind placebo (saline) infusion will be performed during the first PET/MR scan in all subjects, i.e. both arms. In a cross-over study design, esketamine will be administered during the second scan and racemic ketamine during the third scan.	Drug: Placebo; intravenous infusion; Other Names: saline solution; Drug: Ketamine Hydrochloride; intravenous infusion; Other Names: Racemic ketamine (R, S)-Ketamine; Drug: Esketamine; intravenous infusion; Other Names: (S)-Ketamine
Experimental: Racemic ketamine ((R,S)-Ketamine); Single-blind placebo (saline) infusion will be performed during the first PET/MR scan in all subjects, i.e. both arms. In a cross-over study design, racemic ketamine will be administered during the second scan and esketamine during the third scan.	Drug: Placebo; intravenous infusion; Other Names: saline solution; Drug: Ketamine Hydrochloride; intravenous infusion; Other Names: Racemic ketamine (R, S)-Ketamine; Drug: Esketamine; intravenous infusion; Other Names: (S)-Ketamine
Experimental: Pilot study II: Esketamine ((S)-Ketamine); In a cross-over study design, esketamine will be administered during the first scan and placebo during the second scan.	Drug: Pilot study II: Esketamine; intravenous infusion; Other Names: (S)-Ketamine; Drug: Pilot study II: Placebo; intravenous infusion; Other Names: Saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cerebral metabolic rate of glucose (CMRGlu)	Change in CMRGlu between each PET/MR scan	during PETMR/during 45 minutes of infusion
Change in cerebral blood flow (CBF)	Change in CMRGlu between each PET/MR scan	during PETMR/during 45 minutes of infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Positive and Negative Syndrome Scale	Minimum: 30, Maximum: 210; higher score indicates worse outcome	one hour after infusion to baseline
Change in Brief Psychiatric Rating Scale	Minimum: 18, Maximum: 126; higher score indicates worse outcome	one hour after infusion to baseline
Change in Clinician Administered Dissociative States Scale	Minimum: 0, Maximum: 92; higher score indicates worse outcome	one hour after infusion to baseline

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2020
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: October 8, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Ketamine
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Psychotropic Drugs; Antidepressive Agents; Ketamine; Pharmaceutical Solutions; Esketamine
• Other Study ID Numbers: v2_06.02.2024

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