Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter and Its Relevance for Rapid Antidepressant Response
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Medical University of Vienna
- Enrollment
- 74
- Locations
- 1
- Primary Endpoint
- Pilot Study II: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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)
Arms & Interventions
(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
Intervention: (S)-ketamine (Main study) (Drug)
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
Intervention: Placebo (Drug)
(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
Intervention: (S)-ketamine (Pilot II) (Drug)
(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
Intervention: (R,S)-ketamine (Pilot II) (Drug)
(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
Intervention: (R,S)-ketamine (Pilot I) (Drug)
(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
Intervention: (R,S)-ketamine (Pilot III) (Drug)
Outcomes
Primary Outcomes
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: resting state MRI
Time Frame: after PET 2
changes to rsFC and rsfMRI after (R,S)-ketamine
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: MRS
Time Frame: after PET 2
changes to Glutamate, GABA, and metabolites after (R,S)-ketami
Secondary Outcomes
- Change in Hamilton Depression Rating Scale Points(1 day after infusion to baseline)
Investigators
Rupert Lanzenberger
Assoc. Prof. PD Dr. Rupert Lanzenberger, MD
Medical University of Vienna