Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter

Depression Clinical Trial

Official title:

Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter and Its Relevance for Rapid Antidepressant Response

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02717052
• Other study ID #: 1643/2014
• Secondary ID: 2014-003280-38
• Status: Recruiting
• Phase: Phase 2
• Start date: May 2016
• Est. completion date: December 31, 2019

Study information

• Verified date: October 2018
• Source: Medical University of Vienna
• Contact: Rupert Lanzenberger, Prof.
• Phone: 014040035760
• Email: rupert.lanzenberger[@]meduniwien.ac.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Depression
• Ketamine

Intervention

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

Other:
• PILOT Study II: PET1
[11C]DASB PET
• PILOT Study II: PET2
[11C]DASB PET
• Main Study: PET1
[11C]DASB PET
• Main Study: PET2
[11C]DASB PET
• PILOT Study I: PET1
[11C]DASB PET
• 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)
• (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:
• PILOT Study III: PET1
[11C]DASB PET
• PILOT Study III: PET2
[11C]DASB PET

Locations

Country	Name	City	State
Austria	Department of Psychiatry and Psychotherapy, Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pilot Study II: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)	Occupancy assessed using kinetic modeling	during PET/during 135 minutes of infusion
Primary	Pilot Study II: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP)	Occupancy assessed using kinetic modeling	during PET/during 135 minutes of infusion
Primary	Main Study: (S)-ketamine SERT occupancy assessed with DASB binding potential (BP)	Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100	during PET/starting 10 minutes afer 40 minutes of infusion
Primary	Pilot Study I: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP)	Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100	during PET/starting 10 minutes afer 40 minutes of infusion
Primary	Pilot Study III: (R,S)-ketamine SERT occupancy assessed with DASB binding potential (BP)	Occupancy (%)=(1-BPND PET 2 (treatment) / BPND PET 1 (baseline)) x100	during PET
Primary	Pilot Study III: resting state MRI	changes to rsFC and rsfMRI after (R,S)-ketamine	after PET 2
Primary	Pilot Study III: MRS	changes to Glutamate, GABA, and metabolites after (R,S)-ketami	after PET 2
Secondary	Change in Hamilton Depression Rating Scale Points		2 hours after infusion to baseline
Secondary	Change in Hamilton Depression Rating Scale Points		1 day after infusion to baseline