Depression, Ketamine
Conditions
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.
Interventions
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)
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.
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.
DRUGPlacebo
0.9% saline solution i.v. over 40 Minutes (ending 10 minutes before PET measurement)
OTHERPILOT Study II: PET1
\[11C\]DASB PET
OTHERPILOT Study II: PET2
\[11C\]DASB PET
OTHERMain Study: PET1
\[11C\]DASB PET
OTHERMain Study: PET2
\[11C\]DASB PET
OTHERPILOT Study I: PET1
\[11C\]DASB PET
OTHERPILOT 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)
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
OTHERPILOT Study III: PET1
\[11C\]DASB PET
OTHERPILOT Study III: PET2
\[11C\]DASB PET
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Pilot I and Pilot III not randomised
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 MRI | after PET 2 | changes to rsFC and rsfMRI after (R,S)-ketamine |
| Pilot Study III: MRS | after PET 2 | changes to Glutamate, GABA, and metabolites after (R,S)-ketami |
Secondary
| Measure | Time frame |
|---|---|
| Change in Hamilton Depression Rating Scale Points | 2 hours after infusion to baseline |
Countries
Austria
Contacts
Primary ContactRupert Lanzenberger, Prof.
Outcome results
None listed