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

Tracking Information

• First Submitted Date: September 28, 2020
• First Posted Date: October 14, 2020
• Last Update Posted Date: October 14, 2020
• Estimated Study Start Date: October 2020
• Estimated Primary Completion Date: September 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 8, 2020)

• 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
• Change in cerebral blood flow (CBF) [ Time Frame: during PETMR/during 45 minutes of infusion ]
  Change in CMRGlu between each PET/MR scan

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 8, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Imaging Neural Correlates of Ketamine Using PET/MR
• Official Title: Imaging Neural Correlates of Antidepressant Action of Ketamine Stereoisomers Using Pharmacological PET/MR Imaging and Metabolite Analysis.
• 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)
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
• Condition: Major Depressive Disorder

Intervention

• 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

Study Arms

• 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.

  Interventions:

  • Drug: Ketamine Hydrochloride
  • Drug: Esketamine
  • Drug: Placebo
• 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.

  Interventions:

  • Drug: Ketamine Hydrochloride
  • Drug: Esketamine
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: October 8, 2020): 65
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2023
• Estimated Primary Completion Date: September 30, 2023 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04587778
• Other Study ID Numbers: v1.7_21.02.2020
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Rupert Lanzenberger, Medical University of Vienna
• Original Responsible Party: Same as current
• Current Study Sponsor: Medical University of Vienna
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Medical University of Vienna
• Verification Date: October 2020