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Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter

Primary Purpose

Depression, Ketamine

Status
Unknown status
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
(S)-ketamine (Main study)
(S)-ketamine (Pilot II)
(R,S)-ketamine (Pilot II)
Placebo
PILOT Study II: PET1
PILOT Study II: PET2
Main Study: PET1
Main Study: PET2
PILOT Study I: PET1
PILOT Study I: PET2
(R,S)-ketamine (Pilot I)
(R,S)-ketamine (Pilot III)
PILOT Study III: PET1
PILOT Study III: PET2
Sponsored by
Medical University of Vienna
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • Department of Psychiatry and Psychotherapy, Medical University of ViennaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

(S)-ketamine

Placebo

(S)-ketamine (Pilot Study II, 5 subj.)

(R,S)-ketamine (Pilot Study II, 5 subj.)

(R,S)-ketamine (Pilot Study I, 12 subj.)

(R,S)-ketamine (Pilot Study III, 12 subj.)

Arm Description

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

Pilot Study II: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)
Occupancy assessed using kinetic modeling
Pilot Study II: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP)
Occupancy assessed using kinetic modeling
Main Study: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)
Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100
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
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
Pilot Study III: resting state MRI
changes to rsFC and rsfMRI after (R,S)-ketamine
Pilot Study III: MRS
changes to Glutamate, GABA, and metabolites after (R,S)-ketami

Secondary Outcome Measures

Change in Hamilton Depression Rating Scale Points
Change in Hamilton Depression Rating Scale Points

Full Information

First Posted
March 11, 2016
Last Updated
October 12, 2018
Sponsor
Medical University of Vienna
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1. Study Identification

Unique Protocol Identification Number
NCT02717052
Brief Title
Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter
Official Title
Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter and Its Relevance for Rapid Antidepressant Response
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Unknown status
Study Start Date
May 2016 (undefined)
Primary Completion Date
December 31, 2019 (Anticipated)
Study Completion Date
December 31, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Ketamine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Pilot I and Pilot III not randomised
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
74 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
(S)-ketamine
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
(S)-ketamine (Pilot Study II, 5 subj.)
Arm Type
Experimental
Arm Description
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
Arm Title
(R,S)-ketamine (Pilot Study II, 5 subj.)
Arm Type
Experimental
Arm Description
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
Arm Title
(R,S)-ketamine (Pilot Study I, 12 subj.)
Arm Type
Experimental
Arm Description
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
Arm Title
(R,S)-ketamine (Pilot Study III, 12 subj.)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
(S)-ketamine (Main study)
Other Intervention Name(s)
Esketaminhydrochlorid
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
(S)-ketamine (Pilot II)
Other Intervention Name(s)
Esketaminhydrochlorid
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
(R,S)-ketamine (Pilot II)
Other Intervention Name(s)
Ketaminhydrochlorid
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
0.9% saline solution i.v. over 40 Minutes (ending 10 minutes before PET measurement)
Intervention Type
Other
Intervention Name(s)
PILOT Study II: PET1
Intervention Description
[11C]DASB PET
Intervention Type
Other
Intervention Name(s)
PILOT Study II: PET2
Intervention Description
[11C]DASB PET
Intervention Type
Other
Intervention Name(s)
Main Study: PET1
Intervention Description
[11C]DASB PET
Intervention Type
Other
Intervention Name(s)
Main Study: PET2
Intervention Description
[11C]DASB PET
Intervention Type
Other
Intervention Name(s)
PILOT Study I: PET1
Intervention Description
[11C]DASB PET
Intervention Type
Other
Intervention Name(s)
PILOT Study I: PET2
Intervention Description
[11C]DASB PET
Intervention Type
Drug
Intervention Name(s)
(R,S)-ketamine (Pilot I)
Other Intervention Name(s)
Ketaminhydrochlorid
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
(R,S)-ketamine (Pilot III)
Other Intervention Name(s)
Ketaminhydrochlorid
Intervention Description
Ketamin-hameln (Ketaminhydrochlorid) 50mg/ml Ampullen; Hameln Pharma Plus GmbH; Sanova Pharma Dosis: 0.80mg/kg bodyweight i.v. over 50
Intervention Type
Other
Intervention Name(s)
PILOT Study III: PET1
Intervention Description
[11C]DASB PET
Intervention Type
Other
Intervention Name(s)
PILOT Study III: PET2
Intervention Description
[11C]DASB PET
Primary Outcome Measure Information:
Title
Pilot Study II: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)
Description
Occupancy assessed using kinetic modeling
Time Frame
during PET/during 135 minutes of infusion
Title
Pilot Study II: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP)
Description
Occupancy assessed using kinetic modeling
Time Frame
during PET/during 135 minutes of infusion
Title
Main Study: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)
Description
Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100
Time Frame
during PET/starting 10 minutes afer 40 minutes of infusion
Title
Pilot Study I: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP)
Description
Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100
Time Frame
during PET/starting 10 minutes afer 40 minutes of infusion
Title
Pilot Study III: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP)
Description
Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100
Time Frame
during PET
Title
Pilot Study III: resting state MRI
Description
changes to rsFC and rsfMRI after (R,S)-ketamine
Time Frame
after PET 2
Title
Pilot Study III: MRS
Description
changes to Glutamate, GABA, and metabolites after (R,S)-ketami
Time Frame
after PET 2
Secondary Outcome Measure Information:
Title
Change in Hamilton Depression Rating Scale Points
Time Frame
2 hours after infusion to baseline
Title
Change in Hamilton Depression Rating Scale Points
Time Frame
1 day after infusion to baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rupert Lanzenberger, Prof.
Phone
014040035760
Email
rupert.lanzenberger@meduniwien.ac.at
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rupert Lanzenberger, Prof.
Organizational Affiliation
Department of Psychiatry and Psychotherapy, Medical University of Vienna
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Psychiatry and Psychotherapy, Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rupert Lanzenberger, A/Prof.
Phone
+43 40400
Ext
3825
Email
rupert.lanzenberger@meduniwien.ac.at
First Name & Middle Initial & Last Name & Degree
Rupert Lanzenberger, A/Prof. MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29045739
Citation
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.
Results Reference
derived

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Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter

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