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Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

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.

Condition or disease Intervention/treatment Phase
Depression Ketamine Drug: (S)-ketamine (Main study) Drug: (S)-ketamine (Pilot II) Drug: (R,S)-ketamine (Pilot II) Drug: Placebo Other: PILOT Study II: PET1 Other: PILOT Study II: PET2 Other: Main Study: PET1 Other: Main Study: PET2 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 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
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
Official Title: Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter and Its Relevance for Rapid Antidepressant Response
Study Start Date : May 2016
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

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 Name: 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

Drug: Placebo
0.9% saline solution i.v. over 40 Minutes (ending 10 minutes before PET measurement)

Other: Main Study: PET1
[11C]DASB PET

Other: Main Study: PET2
[11C]DASB PET

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 Name: 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

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

Other: PILOT Study II: PET1
[11C]DASB PET

Other: PILOT Study II: PET2
[11C]DASB PET

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 Name: 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 Name: Ketaminhydrochlorid

Other: PILOT Study III: PET1
[11C]DASB PET

Other: PILOT Study III: PET2
[11C]DASB PET




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Pilot Study III: resting state MRI [ Time Frame: after PET 2 ]
    changes to rsFC and rsfMRI after (R,S)-ketamine

  7. Pilot Study III: MRS [ Time Frame: after PET 2 ]
    changes to Glutamate, GABA, and metabolites after (R,S)-ketami


Secondary Outcome Measures :
  1. Change in Hamilton Depression Rating Scale Points [ Time Frame: 2 hours after infusion to baseline ]
  2. Change in Hamilton Depression Rating Scale Points [ Time Frame: 1 day after infusion to baseline ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02717052


Contacts
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Contact: Rupert Lanzenberger, Prof. 014040035760 rupert.lanzenberger@meduniwien.ac.at

Locations
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Austria
Department of Psychiatry and Psychotherapy, Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Rupert Lanzenberger, A/Prof.    +43 40400 ext 3825    rupert.lanzenberger@meduniwien.ac.at   
Principal Investigator: Rupert Lanzenberger, A/Prof. MD         
Sponsors and Collaborators
Medical University of Vienna
Investigators
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Principal Investigator: Rupert Lanzenberger, Prof. Department of Psychiatry and Psychotherapy, Medical University of Vienna
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Rupert Lanzenberger, Assoc. Prof. PD Dr. Rupert Lanzenberger, MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT02717052    
Other Study ID Numbers: 1643/2014
2014-003280-38 ( EudraCT Number )
First Posted: March 23, 2016    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Depression
Behavioral Symptoms
Ketamine
Esketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents
Psychotropic Drugs