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

• ClinicalTrials.gov Identifier: NCT04587778
• Recruitment Status: Not yet recruiting
• First Posted: October 14, 2020
• Last Update Posted: October 14, 2020
• Sponsor: Medical University of Vienna
• Information provided by (Responsible Party): Rupert Lanzenberger, Medical University of Vienna

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Ketamine Hydrochloride; Drug: Esketamine; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Imaging Neural Correlates of Antidepressant Action of Ketamine Stereoisomers Using Pharmacological PET/MR Imaging and Metabolite Analysis.
• Estimated Study Start Date: October 2020
• Estimated Primary Completion Date: September 30, 2023
• Estimated Study Completion Date: September 30, 2023

Arms and Interventions

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: Ketamine Hydrochloride; intravenous infusion; Other Name: Racemic ketamine (R, S)-Ketamine; Drug: Esketamine; intravenous infusion; Other Name: (S)-Ketamine; Drug: Placebo; intravenous infusion; Other Name: saline solution
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: Ketamine Hydrochloride; intravenous infusion; Other Name: Racemic ketamine (R, S)-Ketamine; Drug: Esketamine; intravenous infusion; Other Name: (S)-Ketamine; Drug: Placebo; intravenous infusion; Other Name: saline solution

Outcome Measures

Primary Outcome Measures :

1. Change in Cerebral metabolic rate of glucose (CMRGlu) [ Time Frame: during PETMR/during 45 minutes of infusion ]
   Change in CMRGlu between each PET/MR scan
2. Change in cerebral blood flow (CBF) [ Time Frame: during PETMR/during 45 minutes of infusion ]
   Change in CMRGlu between each PET/MR scan

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Rupert Lanzenberger, Prof., Medical University of Vienna
• ClinicalTrials.gov Identifier: NCT04587778
• Other Study ID Numbers: v1.7_21.02.2020
• First Posted: October 14, 2020
• Last Update Posted: October 14, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rupert Lanzenberger, Medical University of Vienna:

Ketamine

Additional relevant MeSH terms:

Depressive Disorder; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Ketamine; Esketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antidepressive Agents; Psychotropic Drugs