Clinical TrialTreatment-Resistant Depression (TRD)KetaminePlaceboCompleted

A randomised, double blind, active placebo-controlled crossover trial to evaluate the short term efficacy of an N-Methyl-D-Aspartate antagonist for patients with treatment resistant depression

This randomised, double-blind, active placebo-controlled crossover trial (n=30) investigates the short-term efficacy of ketamine for patients with treatment-resistant depression (TRD).

Target Enrollment
30 participants
Study Type
Phase II/III interventional
Design
Randomized, double Blind

Detailed Description

Randomised, double-blind crossover comparing single IV ketamine (bolus 0.25 mg/kg then infusion 0.25 mg/kg/hr for 45 minutes) with an active remifentanil comparator; 3-week washout between sessions.

Primary outcome assessed with MADRS; ancillary measures include plasma BDNF at 4 hours post-intervention and follow-ups at days 1, 7, 14 and 21 during a 42-day study period.

Study Protocol

Preparation

sessions

Dosing

2 sessions
45 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Single IV ketamine session (bolus + short infusion) as active treatment in crossover.

Interventions

  • Ketamine0.25 mg/kg
    via IV• single dose• 1 doses total

    IV bolus 0.25 mg/kg then infusion 0.25 mg/kg/hr for 45 minutes.

Remifentanil

active comparator

Active placebo comparator using remifentanil target-controlled infusion.

Interventions

  • Placebo0.1 ng/ml
    via IV• single dose• 1 doses total

    Target effect-site concentration 0.1 ng/ml using Minto pharmacokinetic model for ~8 minutes.

Participants

Ages
18 – 60
Sexes
Male & Female

Inclusion Criteria

  • Participant is willing and able to give informed consent for participation in the trial.
  • Male or female, aged 18 years or above and less than 60.
  • In the Investigators’ opinion, is able and willing to comply with all trial requirements.
  • Major depressive disorder for at least three months, as assessed by a Clinical Interview using DSM-IV criteria.
  • MADRS >20.
  • An inadequate response to at least two antidepressant courses (Antidepressant Treatment History Form) one of which can include the current episode.
  • Stable on antidepressant medication for four weeks prior to Study Day 1.

Exclusion Criteria

  • Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
  • Significant renal or hepatic impairment.
  • Cardiovascular conditions including abnormal heart rate and blood pressure checked at screening.
  • Participants who have participated in another research trial involving an investigational product in the past 12 weeks.
  • History of psychosis.
  • Any unstable medical or neurologic condition.
  • Planned major changes to psychotropic medication.
  • Imminent risk of suicide as determined by the CSSRS.
  • Planned or probable use of ECT.
  • Substance abuse or dependence in previous 6 months.
  • Any history of abuse of ketamine or phencyclidine.
  • Contraindication to the use of ketamine according to manufacturer guidelines.
  • Planned use of ketamine, for example, for pain control.
  • Unable to fast for four hours prior to each administration of trial drug.
  • Any other condition judged by the treating clinician as likely to impact on the ability of the participant to complete the trial.
  • Body-weight <50kg or >120kg.
  • Current use of NMDA antagonist medications (e.g. memantine / amantadine / rimantadine / lamotrigine / dextromethorphan/procyclidine).
  • Inability to speak or read English.
  • Contraindications for MRI scanning.

Study Details

Locations

Unknown facility — Australia

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