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Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter

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ClinicalTrials.gov Identifier: NCT02717052
Recruitment Status : Unknown
Verified October 2018 by Rupert Lanzenberger, Medical University of Vienna.
Recruitment status was:  Recruiting
First Posted : March 23, 2016
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
Rupert Lanzenberger, Medical University of Vienna

Tracking Information
First Submitted Date  ICMJE March 11, 2016
First Posted Date  ICMJE March 23, 2016
Last Update Posted Date October 15, 2018
Study Start Date  ICMJE May 2016
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2017)
  • Pilot Study II: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP) [ Time Frame: during PET/during 135 minutes of infusion ]
    Occupancy assessed using kinetic modeling
  • Pilot Study II: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP) [ Time Frame: during PET/during 135 minutes of infusion ]
    Occupancy assessed using kinetic modeling
  • Main Study: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP) [ Time Frame: during PET/starting 10 minutes afer 40 minutes of infusion ]
    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) [ Time Frame: during PET/starting 10 minutes afer 40 minutes of infusion ]
    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) [ Time Frame: during PET ]
    Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100
  • Pilot Study III: resting state MRI [ Time Frame: after PET 2 ]
    changes to rsFC and rsfMRI after (R,S)-ketamine
  • Pilot Study III: MRS [ Time Frame: after PET 2 ]
    changes to Glutamate, GABA, and metabolites after (R,S)-ketami
Original Primary Outcome Measures  ICMJE
 (submitted: March 22, 2016)
  • Pilot Study: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP) [ Time Frame: during PET/during 135 minutes of infusion ]
    Occupancy assessed using kinetic modeling
  • Pilot Study: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP) [ Time Frame: during PET/during 135 minutes of infusion ]
    Occupancy assessed using kinetic modeling
  • Main Study: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP) [ Time Frame: during PET/starting 10 minutes afer 40 minutes of infusion ]
    Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100
  • Change in Hamilton Depression Rating Scale Points [ Time Frame: 2 hours after infusion to baseline ]
  • Change in Hamilton Depression Rating Scale Points [ Time Frame: 1 day after infusion to baseline ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2016)
  • Change in Hamilton Depression Rating Scale Points [ Time Frame: 2 hours after infusion to baseline ]
  • Change in Hamilton Depression Rating Scale Points [ Time Frame: 1 day after infusion to baseline ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter
Official Title  ICMJE Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter and Its Relevance for Rapid Antidepressant Response
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Pilot I and Pilot III not randomised
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Depression
  • Ketamine
Intervention  ICMJE
  • 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 Name: Esketaminhydrochlorid
  • 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 Name: Esketaminhydrochlorid
  • 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 Name: Ketaminhydrochlorid
  • Drug: Placebo
    0.9% saline solution i.v. over 40 Minutes (ending 10 minutes before PET measurement)
  • Other: PILOT Study II: PET1
    [11C]DASB PET
  • Other: PILOT Study II: PET2
    [11C]DASB PET
  • Other: Main Study: PET1
    [11C]DASB PET
  • Other: Main Study: PET2
    [11C]DASB PET
  • 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 Name: Ketaminhydrochlorid
  • 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 Name: Ketaminhydrochlorid
  • Other: PILOT Study III: PET1
    [11C]DASB PET
  • Other: PILOT Study III: PET2
    [11C]DASB PET
Study Arms  ICMJE
  • 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

    Interventions:
    • Drug: (S)-ketamine (Main study)
    • Other: Main Study: PET1
    • Other: Main Study: PET2
  • 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

    Interventions:
    • Drug: Placebo
    • Other: Main Study: PET1
    • Other: Main Study: PET2
  • 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

    Interventions:
    • Drug: (S)-ketamine (Pilot II)
    • Other: PILOT Study II: PET1
    • Other: PILOT Study II: PET2
  • 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

    Interventions:
    • Drug: (R,S)-ketamine (Pilot II)
    • Other: PILOT Study II: PET1
    • Other: PILOT Study II: PET2
  • 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

    Interventions:
    • Other: PILOT Study I: PET1
    • Other: PILOT Study I: PET2
    • Drug: (R,S)-ketamine (Pilot I)
  • 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

    Interventions:
    • Drug: (R,S)-ketamine (Pilot III)
    • Other: PILOT Study III: PET1
    • Other: PILOT Study III: PET2
Publications * Spies M, James GM, Berroterán-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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 18, 2017)
74
Original Estimated Enrollment  ICMJE
 (submitted: March 22, 2016)
50
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02717052
Other Study ID Numbers  ICMJE 1643/2014
2014-003280-38 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Rupert Lanzenberger, Medical University of Vienna
Study Sponsor  ICMJE Medical University of Vienna
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rupert Lanzenberger, Prof. Department of Psychiatry and Psychotherapy, Medical University of Vienna
PRS Account Medical University of Vienna
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP