Clinical TrialTreatment-Resistant Depression (TRD)KetamineKetamineKetaminePlaceboCompleted

Ketamine for Treatment Resistant Late-Life Depression

The purpose of this study is to examine the effectiveness of a single infusion of ketamine (KET), to determine which dose is optimal 7 days after infusion using Bayesian Adaptive Randomization, and to learn about how ketamine works in the body and brain in persons with late-life treatment resistant depression.

Target Enrollment
33 participants
Study Type
Phase III interventional
Design
Randomized, quadruple Blind

Detailed Description

Randomized, quadruple-blind, Bayesian adaptive parallel-group design in veterans with late-life treatment-resistant depression (actual N=33) comparing single 40‑minute IV infusions of ketamine 0.10, 0.25, 0.50 mg/kg and midazolam 0.03 mg/kg.

Primary outcome is MADRS response (≥50% improvement) at 7 days; adaptive randomization aims to identify the best-performing ketamine dose. Durability assessed to 4 weeks; safety/tolerability monitored acutely and during follow-up.

Exploratory measures include neurocognitive testing, peripheral biomarkers of plasticity/inflammation, and resting-state quantitative EEG.

Study Protocol

Preparation

sessions

Dosing

1 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine 0.10 mg/kg

experimental

Single 40 min IV infusion of ketamine 0.10 mg/kg

Interventions

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

    40 min infusion

Ketamine 0.25 mg/kg

experimental

Single 40 min IV infusion of ketamine 0.25 mg/kg

Interventions

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

    40 min infusion

Ketamine 0.50 mg/kg

experimental

Single 40 min IV infusion of ketamine 0.50 mg/kg

Interventions

  • Ketamine0.5 mg/kg
    via IV• single dose• 1 doses total

    40 min infusion

Midazolam 0.03 mg/kg

active comparator

Single 40 min IV infusion of midazolam 0.03 mg/kg (active placebo)

Interventions

  • Placebo0.03 mg/kg
    via IV• single dose• 1 doses total

    Midazolam 0.03 mg/kg, active comparator; 40 min infusion

Participants

Ages
55 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Male or female patients, 55 years of age,
  • Participants must fulfill DSM 5 criteria for a Major Depressive Episode (Unipolar), based on a structured diagnostic interview, the DSM 5 M.I.N.I. 7.0
  • Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration),
  • Participants have not responded to two or more adequate trials of FDA-approved antidepressants, determined by Antidepressant Treatment Response Questionnaire (ATRQ) criteria.
  • Participants must score 14 or greater on the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), and score 27 on the Montgomery Asberg Depression Rating Scale (MADRS),
  • Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document.

Exclusion Criteria

  • Exclusion Criteria:
  • Patients currently on fluoxetine,
  • History of schizophrenia, schizoaffective disorder or any psychotic disorder, or bipolar disorder,
  • Documented history of a psychotic disorder in a first-degree relative,
  • Current diagnosis of obsessive-compulsive disorder (OCD) or eating disorder [bulimia nervosa or anorexia nervosa],
  • Alcohol or substance use [except nicotine] within the preceding 6 months,
  • Patients with any clinically significant personality disorder that would, in the investigator's judgment, preclude safe study participation,
  • Patients judged to be at serious and imminent suicidal or homicidal risk,
  • Serious, unstable medical illnesses including respiratory [obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics], cardiovascular [including ischemic heart disease and uncontrolled hypertension], and neurologic [including history of severe head injury],
  • For study entry, patients must be reasonable medical candidates for ketamine or midazolam infusion, as determined by a board-certified physician co-investigator during study Screening,
  • Clinically significant abnormal findings of laboratory parameters [including urine toxicology screen for drugs of abuse], physical examination, or ECG,
  • Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg),
  • Patients with one or more 11 seizures without a clear and resolved etiology,
  • Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening,
  • Past intolerance or hypersensitivity to ketamine, or history of recreational use of phencyclidine (PCP) or ketamine,
  • Past intolerance or hypersensitivity to midazolam,
  • Age-related cognitive decline or mild dementia suggested by a score of < 25 on the Mini-Mental State Examination (MMSE) at Screening,
  • Patients taking medications with known activity at the N-methyl-D-aspartate receptor (NMDA) or AMPA glutamate receptor [e.g., riluzole, amantadine, lamotrigine, memantine, topiramate, dextromethorphan, D-cycloserine], or the muopioid receptor,
  • Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide,
  • Patients who demonstrate > 25% decrease in depressive symptoms as reflected by the QIDS-SR score from Screening to Randomization,
  • Patients who have received electroconvulsive therapy (ECT) in the past 6 months prior to Screening,
  • Patients currently receiving treatment with vagus nerve stimulation (VNS) or repetitive transcranial stimulation (rTMS).

Study Details

Locations

Michael E. DeBakey VA Medical Center, Houston, TX — Houston, Texas, United States

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