Imaging Neural Correlates of Ketamine Using PET/MR

Study Overview
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Brief Summary
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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)

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

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Ketamine Hydrochloride
* Drug: Esketamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esketamine ((S)-Ketamine)<br>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<br>* intravenous infusion<br>* Other names: Racemic ketamine (R, S)-Ketamine;Drug: Esketamine<br>* intravenous infusion<br>* Other names: (S)-Ketamine;Drug: Placebo<br>* intravenous infusion<br>* Other names: saline solution;|
| Experimental: Racemic ketamine ((R,S)-Ketamine)<br>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<br>* intravenous infusion<br>* Other names: Racemic ketamine (R, S)-Ketamine;Drug: Esketamine<br>* intravenous infusion<br>* Other names: (S)-Ketamine;Drug: Placebo<br>* intravenous infusion<br>* Other names: saline solution;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine