Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter

Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter and Its Relevance for Rapid Antidepressant Response

The study at hand is the first to investigate ketamine's SERT binding in humans, by utilizing the highly selective SERT radioligand [11C]DASB and positron emission tomography.

Study Overview

• Status: Unknown
• Conditions: Depression; Ketamine
• Intervention / Treatment: Drug: (S)-ketamine (Main study); Other: Main Study: PET1; Other: Main Study: PET2; Drug: Placebo; Drug: (S)-ketamine (Pilot II); Other: PILOT Study II: PET1; Other: PILOT Study II: PET2; Drug: (R,S)-ketamine (Pilot II); Other: PILOT Study I: PET1; Other: PILOT Study I: PET2; Drug: (R,S)-ketamine (Pilot I); Drug: (R,S)-ketamine (Pilot III); Other: PILOT Study III: PET1; Other: PILOT Study III: PET2

Detailed Description

Intravenous application of ketamine is currently dramatically gaining in significance as a rapid and highly effective antidepressant treatment option. Ketamine modulates various neurotransmitter systems, though the mechanisms responsible for its antidepressant effects remain unkownn. However, the serotonin transporter (SERT) presents a target of high interest due to the SERT's fundamental role in depression's pathophysiology as well as in antidepressant response. The study at hand is the first to investigate ketamine's SERT binding in humans, by utilizing the highly selective SERT radioligand [11C]DASB and positron emission tomography. Further, investigation of severely depressed patients provides the unique opportunity to establish the relationship between ketamine's SERT binding and its antidepressant efficacy.

• Study Type: Interventional
• Enrollment (Anticipated): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Department of Psychiatry and Psychotherapy, Medical University of Vienna
    • Contact: Rupert Lanzenberger, A/Prof.; Phone Number: 3825 +43 40400; Email: rupert.lanzenberger@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-55 years
• somatic health
• severe unipolar depression according to DSM-IV (SCID) und HAM-D (for patients)
• capable of giving informed consent
• negative pregnancy test (females)

Exclusion Criteria:

• severe somatic illness
• psychiatric disorder (for healthy controls)
• an axis I comorbidity other than MDD , other than anxiety symptoms (for patients)
• clinically relevant alterations in blood draw, ecg, and somatic testing
• substance dependency disorder
• intake of psychopharmacological medication in last 6 months
• first degree relative with Axis 1 disorder (for Pilot I study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: (S)-ketamine; Ketanest® S (Esketaminhydrochlorid) 5mg/ml and 25mg/ml ampoules; Actavis Italy S.P.A./Pfizer Corporation Austria GmbH Dosis: 0.25mg/kg bodyweight i.v. over 40 Minutes (ending 10 minutes before PET measurement) all patients and 10 HC (randomized, double blind) Interventions: Drug: (S)-ketamine (Main study) Other: Main study: PET1 Other: Main study: PET2	Drug: (S)-ketamine (Main study); Ketanest® S (Esketaminhydrochlorid) 5mg/ml and 25mg/ml ampoules; Actavis Italy S.P.A./Pfizer Corporation Austria GmbH Dosis: 0.25mg/kg bodyweight i.v. over 40 Minutes (ending 10 minutes before PET measurement); Other Names: Esketaminhydrochlorid; Other: Main Study: PET1; [11C]DASB PET; Other: Main Study: PET2; [11C]DASB PET
Placebo Comparator: Placebo; 0.9% saline solution i.v. over 40 Minutes (ending 10 minutes before PET measurement) 10 HC (randomized, double blind) Interventions: Drug: Placebo Other: Main study: PET1 Other: Main study: PET2	Other: Main Study: PET1; [11C]DASB PET; Other: Main Study: PET2; [11C]DASB PET; Drug: Placebo; 0.9% saline solution i.v. over 40 Minutes (ending 10 minutes before PET measurement)
Experimental: (S)-ketamine (Pilot Study II, 5 subj.); Ketanest® S (Esketaminhydrochlorid) 5mg/ml and 25mg/ml ampoules; Actavis Italy S.P.A./Pfizer Corporation Austria GmbH Dosis: 0.10mg/kg bodyweight bolus applied over 5 minutes (starting 15 minutes before PET measurement) and continuous infusion of 0.30mg/kg bodyweight applied over the course of 130 minutes. Pilot-study II is cross-over design! Interventions: Drug: (S)-ketamine (Pilot II) Other: PILOT Study II: PET1 Other: PILOT Study II: PET2	Drug: (S)-ketamine (Pilot II); Ketanest® S (Esketaminhydrochlorid) 5mg/ml and 25mg/ml ampoules; Actavis Italy S.P.A./Pfizer Corporation Austria GmbH Dosis: 0.10mg/kg bodyweight i.v. bolus applied over 5 minutes (starting 15 minutes before PET measurement) and continuous infusion of 0.30mg/kg bodyweight i.v. applied over the course of 130 minutes.; Other Names: Esketaminhydrochlorid; Other: PILOT Study II: PET1; [11C]DASB PET; Other: PILOT Study II: PET2; [11C]DASB PET
Experimental: (R,S)-ketamine (Pilot Study II, 5 subj.); Ketamin-hameln (Ketaminhydrochlorid) 50mg/ml Ampullen; Hameln Pharma Plus GmbH; Sanova Pharma Dosis: 0.20mg/kg bodyweight bolus applied over 5 minutes (starting 15 minutes before PET measurement) and continuous infusion of 0.60mg/kg bodyweight applied over the course of 130 minutes. Pilot-study II is cross-over design! Interventions: Drug: (R,S)-ketamine (Pilot II) Other: PILOT Study II: PET1 Other: PILOT Study II: PET2	Other: PILOT Study II: PET1; [11C]DASB PET; Other: PILOT Study II: PET2; [11C]DASB PET; Drug: (R,S)-ketamine (Pilot II); Ketamin-hameln (Ketaminhydrochlorid) 50mg/ml Ampullen; Hameln Pharma Plus GmbH; Sanova Pharma Dosis: 0.20mg/kg bodyweight i.v. bolus applied over 5 minutes (starting 15 minutes before PET measurement) and continuous infusion of 0.60mg/kg bodyweight applied i.v. over the course of 130 minutes.; Other Names: Ketaminhydrochlorid
Experimental: (R,S)-ketamine (Pilot Study I, 12 subj.); Ketamin-hameln (Ketaminhydrochlorid) 50mg/ml Ampullen; Hameln Pharma Plus GmbH; Sanova Pharma Dosis: 0.50mg/kg bodyweight i.v. over 40 Minutes (ending 5 minutes before PET measurement) Interventions: Drug: (R,S)-ketamine (Pilot I) Other: PILOT Study I: PET1 Other: PILOT Study I: PET2	Other: PILOT Study I: PET1; [11C]DASB PET; Other: PILOT Study I: PET2; [11C]DASB PET; Drug: (R,S)-ketamine (Pilot I); Ketamin-hameln (Ketaminhydrochlorid) 50mg/ml Ampullen; Hameln Pharma Plus GmbH; Sanova Pharma Dosis: 0.50mg/kg bodyweight i.v. over 40 Minutes (ending 10 minutes before PET measurement); Other Names: Ketaminhydrochlorid
Experimental: (R,S)-ketamine (Pilot Study III, 12 subj.); Ketamin-hameln (Ketaminhydrochlorid) 50mg/ml Ampullen; Hameln Pharma Plus GmbH; Sanova Pharma Dosis: 0.80mg/kg bodyweight i.v. over 50 Minutes Interventions: Drug: (R,S)-ketamine (Pilot III) Other: PILOT Study III: PET1 Other: PILOT Study III: PET2	Drug: (R,S)-ketamine (Pilot III); Ketamin-hameln (Ketaminhydrochlorid) 50mg/ml Ampullen; Hameln Pharma Plus GmbH; Sanova Pharma Dosis: 0.80mg/kg bodyweight i.v. over 50; Other Names: Ketaminhydrochlorid; Other: PILOT Study III: PET1; [11C]DASB PET; Other: PILOT Study III: PET2; [11C]DASB PET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pilot Study II: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)	Occupancy assessed using kinetic modeling	during PET/during 135 minutes of infusion
Pilot Study II: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP)	Occupancy assessed using kinetic modeling	during PET/during 135 minutes of infusion
Main Study: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)	Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100	during PET/starting 10 minutes afer 40 minutes of infusion
Pilot Study I: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP)	Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100	during PET/starting 10 minutes afer 40 minutes of infusion
Pilot Study III: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP)	Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100	during PET
Pilot Study III: resting state MRI	changes to rsFC and rsfMRI after (R,S)-ketamine	after PET 2
Pilot Study III: MRS	changes to Glutamate, GABA, and metabolites after (R,S)-ketami	after PET 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Hamilton Depression Rating Scale Points	2 hours after infusion to baseline
Change in Hamilton Depression Rating Scale Points	1 day after infusion to baseline

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Rupert Lanzenberger, Prof., Department of Psychiatry and Psychotherapy, Medical University of Vienna

Publications and helpful links

General Publications

• Spies M, James GM, Berroteran-Infante N, Ibeschitz H, Kranz GS, Unterholzner J, Godbersen M, Gryglewski G, Hienert M, Jungwirth J, Pichler V, Reiter B, Silberbauer L, Winkler D, Mitterhauser M, Stimpfl T, Hacker M, Kasper S, Lanzenberger R. Assessment of Ketamine Binding of the Serotonin Transporter in Humans with Positron Emission Tomography. Int J Neuropsychopharmacol. 2018 Feb 1;21(2):145-153. doi: 10.1093/ijnp/pyx085.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: March 11, 2016
• First Submitted That Met QC Criteria: March 22, 2016
• First Posted (Estimate): March 23, 2016

Study Record Updates

• Last Update Posted (Actual): October 15, 2018
• Last Update Submitted That Met QC Criteria: October 12, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; 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; Esketamine
• Other Study ID Numbers: 1643/2014; 2014-003280-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided