Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter

Medical University of Vienna

Status and phase: Unknown; Phase 2

Conditions: Ketamine; Depression

Treatments: Other: PILOT Study II: PET2; Other: Main Study: PET2; Drug: (R,S)-ketamine (Pilot III); Drug: (R,S)-ketamine (Pilot I); Other: Main Study: PET1; Other: PILOT Study I: PET1; Drug: Placebo; Other: PILOT Study I: PET2; Drug: (S)-ketamine (Pilot II); Other: PILOT Study III: PET1; Drug: (R,S)-ketamine (Pilot II); Other: PILOT Study III: PET2; Other: PILOT Study II: PET1; Drug: (S)-ketamine (Main study)

Study type: Interventional

Funder types: Other

Identifiers

NCT02717052

2014-003280-38 (EudraCT Number)

1643/2014

Details and patient eligibility

About

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.

Full 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.

Enrollment: 74 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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74 participants in 6 patient groups, including a placebo group

(S)-ketamine

Experimental group

Description:

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

Treatment:

Drug: (S)-ketamine (Main study)

Other: Main Study: PET1

Other: Main Study: PET2

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: Main Study: PET1

Other: Main Study: PET2

Drug: Placebo

(S)-ketamine (Pilot Study II, 5 subj.)

Experimental group

Description:

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

Treatment:

Other: PILOT Study II: PET1

Drug: (S)-ketamine (Pilot II)

Other: PILOT Study II: PET2

(R,S)-ketamine (Pilot Study II, 5 subj.)

Experimental group

Description:

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

Treatment:

Other: PILOT Study II: PET1

Drug: (R,S)-ketamine (Pilot II)

Other: PILOT Study II: PET2

(R,S)-ketamine (Pilot Study I, 12 subj.)

Experimental group

Description:

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

Treatment:

Other: PILOT Study I: PET1

Other: PILOT Study I: PET2

Drug: (R,S)-ketamine (Pilot I)

(R,S)-ketamine (Pilot Study III, 12 subj.)

Experimental group

Description:

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

Treatment:

Other: PILOT Study III: PET2

Drug: (R,S)-ketamine (Pilot III)

Other: PILOT Study III: PET1