Clinical TrialTreatment-Resistant Depression (TRD)KetaminePlaceboCompleted

Intravenous ketamine for Treatment Resistant Depression: Exploring biomarkers of response and relapse A double-blind, randomized controlled trial

Double-blind, randomised, placebo-controlled Phase II trial (n=120) evaluating a single intravenous ketamine infusion versus placebo in patients with treatment-resistant depression and bipolar depression, with biomarker and relapse endpoints.

Target Enrollment
120 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

Randomised, double-blind, parallel-group study comparing intravenous ketamine (Ketalar) to placebo in adults with treatment-resistant major depressive disorder or bipolar depression; designed to replicate ketamine efficacy and identify biomarkers of response and relapse.

Primary efficacy assessments occur at screening/day 1, after the IV ketamine injection (day 8), final visit (day 15) and follow-up (day 21). Secondary measures include experience sampling, biomarkers predictive of response and relapse, and psychophysiology of stress.

Study Protocol

Preparation

sessions

Dosing

1 sessions
240 min each

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Ketamine IV

experimental

Intravenous ketamine infusion (Ketalar) as active intervention.

Interventions

  • Ketamine
    via IV• single dose

    Intravenous infusion (Ketalar, Pfizer); dose per protocol

Placebo IV

inactive

Intravenous placebo (solution for infusion) matching ketamine.

Interventions

  • Placebo
    via IV• single dose

    Placebo solution for infusion (intravenous)

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Must be ≥18 years old and meet DSM-IV-TR criteria for Major Depressive Disorder (without psychotic features) or Bipolar Disorder I or II currently in a depressive episode.
  • Bipolar patients must not be in a current mixed episode or have mood-incongruent psychotic features for at least 4 weeks.
  • Medically stable by physical exam, 12-lead ECG and laboratory tests judged not clinically significant by investigator.
  • HAMD-17 total score ≥17 at screening and/or day 1 (predose).
  • MDD patients must have failed ≥2 adequate antidepressant courses (one in current episode); recent starts allowed if minimal improvement after 4 weeks.
  • Dose changes of existing antidepressants require 2 weeks before screening; a 14-day washout applies for recently stopped antidepressants.
  • ECT permitted if ≥2 weeks since last ECT; bipolar participants must be on stable mood-stabilising medication for ≥4 weeks where applicable.
  • Concurrent antidepressant doses should remain stable for study duration; benzodiazepines permitted after clinician consultation.
  • Inpatient or outpatient willing to be admitted for IV ketamine administration and remain at site for 4 hours post-dose.
  • Non-insulin-dependent diabetes adequately controlled permitted.
  • Prior anaesthetic ketamine exposure permitted if not previously enrolled in another ketamine clinical trial.
  • Women of childbearing potential and heterosexually active men must use effective contraception during the study and for 1 month after last dose; negative pregnancy tests required at screening and predose.
  • Willing and able to adhere to protocol and provide informed consent.

Exclusion Criteria

  • History of drug or alcohol abuse or dependence (DSM-IV) within 6 months prior to screening, except nicotine or caffeine.
  • Positive drug-of-abuse screen at screening or day 1 (exceptions may apply for prescribed medications with no abuse history).
  • Positive repeat alcohol breath test is exclusionary.
  • Taking >4 psychotropic medications at day 1 (predose).
  • Autoimmune disorder requiring immunomodulatory therapies may be excluded per investigator judgment.
  • Significant cardiovascular, respiratory, neurological (including seizures), renal, hepatic, endocrine, or immunologic disease within 6 months, glaucoma, or abnormal/uncontrolled thyroid function unless stable on treatment.
  • Uncontrolled hypertension (diastolic >90 mmHg) at screening or day 8.
  • Planned vaccination within 2 weeks before first dose through 2 weeks after last dose.
  • Acute infection based on laboratory assessment unless investigator judges no risk.
  • Systemic corticosteroids within 21 days before day 1.
  • Known allergy, hypersensitivity or contraindication to ketamine or excipients.
  • Receipt of an investigational drug/device within 3 months or current participation in an investigational study.
  • Pregnant or breastfeeding women.
  • Any condition that would, in the investigator's opinion, compromise subject well-being or study participation.
  • Donation of ≥1 unit blood or equivalent acute blood loss within 90 days prior to dosing.
  • Employees or family members of the investigator or study centre with direct involvement in the study.

Study Details

Locations

Belgium

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