Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter

Medical University of Vienna74 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Depression Ketamine

Interventions

(S)-ketamine (Main study)DRUG

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)

(S)-ketamine (Pilot II)DRUG

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.

(R,S)-ketamine (Pilot II)DRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Locations (1)

Department of Psychiatry and Psychotherapy, Medical University of Vienna

Vienna, Austria

RECRUITING

Outcomes

Primary Outcomes

Pilot Study II: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)

Occupancy assessed using kinetic modeling

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: during PET

Pilot Study III: resting state MRI

changes to rsFC and rsfMRI after (R,S)-ketamine

Time frame: after PET 2

Pilot Study III: MRS

changes to Glutamate, GABA, and metabolites after (R,S)-ketami

Time frame: after PET 2

Secondary Outcomes

Central Contacts

Rupert Lanzenberger, Prof.

CONTACT

014040035760 rupert.lanzenberger@meduniwien.ac.at

Data from ClinicalTrials.gov

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