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

Medical University of Vienna

Status and phase: Enrolling; Phase 1

Conditions: Major Depressive Disorder

Treatments: Drug: Pilot study II: Placebo; Drug: Ketamine Hydrochloride; Drug: Placebo; Drug: Esketamine; Drug: Pilot study II: Esketamine

Study type: Interventional

Funder types: Other

Identifiers

NCT04587778

v2_06.02.2024

Details and patient eligibility

About

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.

Enrollment: 65 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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65 participants in 3 patient groups

Esketamine ((S)-Ketamine)

Experimental group

Description:

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.

Treatment:

Drug: Esketamine

Drug: Placebo

Drug: Ketamine Hydrochloride

Racemic ketamine ((R,S)-Ketamine)

Experimental group

Description:

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.

Treatment:

Drug: Esketamine

Drug: Placebo

Drug: Ketamine Hydrochloride

Pilot study II: Esketamine ((S)-Ketamine)

Experimental group

Description:

In a cross-over study design, esketamine will be administered during the first scan and placebo during the second scan.

Treatment:

Drug: Pilot study II: Esketamine

Drug: Pilot study II: Placebo