Clinical TrialMajor Depressive Disorder (MDD)EsketaminePlaceboEsketamineKetamineKetamineKetamineUnknown status

Positron Emission Tomography Assessment of Ketamine Binding of the Serotonin Transporter

Randomized, quadruple-blind PET study (n≈74) comparing (S)-ketamine 0.25 mg/kg i.v. vs saline to assess ketamine binding to SERT with [11C]DASB in severe depression.

Target Enrollment
74 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

This study uses [11C]DASB PET to measure serotonin transporter binding after intravenous ketamine (multiple substudies including a main randomized double-blind esketamine vs saline comparison and several pilot dosing regimens of R,S- and S-ketamine).

Outcomes include PET SERT binding measures and the relationship between ketamine-induced SERT changes and antidepressant efficacy in severely depressed patients; multiple dosing regimens include bolus+infusion and single infusions timed before PET acquisition.

Study Arms & Interventions

(S)-ketamine (Main)

experimental

Esketamine infusion (main study) 0.25 mg/kg i.v. vs saline, single infusion before PET.

Interventions

  • Esketamine0.25 mg/kg
    via IV• single dose

    0.25 mg/kg i.v. infusion over 40 minutes (ending ~10 minutes before PET)

Placebo

inactive

0.9% saline i.v. comparator

Interventions

  • Placebo
    via IV• single dose

    0.9% saline i.v. over 40 minutes (ending ~10 minutes before PET)

(S)-ketamine (Pilot II)

experimental

Esketamine bolus + infusion in crossover Pilot II (5 subjects).

Interventions

  • Esketamine0.1 mg/kg
    via IV• single dose

    0.10 mg/kg bolus over 5 min (start ~15 min before PET) plus 0.30 mg/kg infusion over 130 minutes (crossover)

(R,S)-ketamine (Pilot II)

experimental

R,S-ketamine bolus + infusion in crossover Pilot II (5 subjects).

Interventions

  • Ketamine0.2 mg/kg
    via IV• single dose

    0.20 mg/kg bolus over 5 min (start ~15 min before PET) plus 0.60 mg/kg infusion over 130 minutes (crossover)

(R,S)-ketamine (Pilot I)

experimental

R,S-ketamine single infusion Pilot I (12 subjects).

Interventions

  • Ketamine0.5 mg/kg
    via IV• single dose

    0.50 mg/kg i.v. over 40 minutes (ending ~10 minutes before PET)

(R,S)-ketamine (Pilot III)

experimental

R,S-ketamine single infusion Pilot III (12 subjects).

Interventions

  • Ketamine0.8 mg/kg
    via IV• single dose

    0.80 mg/kg i.v. over 50 minutes

Participants

Ages
18 – 55
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 18-55 years
  • somatic health
  • severe unipolar depression according to DSM-IV (SCID) and HAM-D (for patients)
  • capable of giving informed consent
  • negative pregnancy test (females)

Exclusion Criteria

  • 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 I disorder (for Pilot I study)

Study Details

Locations

Department of Psychiatry and Psychotherapy, Medical University of Vienna — Vienna, Austria

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