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Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter

Phase 2
Conditions
Depression
Ketamine
Interventions
Drug: Placebo
Drug: (R,S)-ketamine (Pilot II)
Drug: (R,S)-ketamine (Pilot I)
Drug: (R,S)-ketamine (Pilot III)
Drug: (S)-ketamine (Main study)
Drug: (S)-ketamine (Pilot II)
Registration Number
NCT02717052
Lead Sponsor
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.

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
74
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)
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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)
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo0.9% 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
(R,S)-ketamine (Pilot Study II, 5 subj.)(R,S)-ketamine (Pilot II)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
(R,S)-ketamine (Pilot Study I, 12 subj.)(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 5 minutes before PET measurement) Interventions: Drug: (R,S)-ketamine (Pilot I) Other: PILOT Study I: PET1 Other: PILOT Study I: PET2
(R,S)-ketamine (Pilot Study III, 12 subj.)(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 Minutes Interventions: Drug: (R,S)-ketamine (Pilot III) Other: PILOT Study III: PET1 Other: PILOT Study III: PET2
(S)-ketamine(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) all patients and 10 HC (randomized, double blind) Interventions: Drug: (S)-ketamine (Main study) Other: Main study: PET1 Other: Main study: PET2
(S)-ketamine (Pilot Study II, 5 subj.)(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 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
Primary Outcome Measures
NameTimeMethod
Pilot Study II: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)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)during PET/during 135 minutes of infusion

Occupancy assessed using kinetic modeling

Main Study: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)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)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)during PET

Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100

Pilot Study III: resting state MRIafter PET 2

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

Pilot Study III: MRSafter PET 2

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

Secondary Outcome Measures
NameTimeMethod
Change in Hamilton Depression Rating Scale Points1 day after infusion to baseline

Trial Locations

Locations (1)

Department of Psychiatry and Psychotherapy, Medical University of Vienna

🇦🇹

Vienna, Austria

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