Clinical TrialNeurological InjuryKetaminePlaceboRecruiting

Ketamine to Treat Patients With Post-comatose Disorders of Consciousness

This double-blind, placebo-controlled crossover trial (n=30) tests intravenous subanesthetic ketamine (TCI to 0.75 µg/ml) versus saline in patients with disorders of consciousness, with TMS-EEG and multimodal imaging assessments.

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

Detailed Description

Randomized, double-blind, placebo-controlled crossover design enrolling 30 patients with disorders of consciousness (UWS or MCS). Each participant receives two infusion sessions five days apart (ketamine and saline, order randomized). TCI is used to target a subanesthetic plasma concentration up to 0.75 µg/ml during infusion (up to 90 minutes).

Neurophysiological measures include TMS-EEG performed from 20 minutes before infusion up to the 90-minute maximum, and multimodal baseline imaging (fMRI, PET, EEG). Primary outcomes are emergence of new conscious behaviours (SECONDs/CRS-R) and increases in brain complexity; secondary outcomes compare baseline imaging and physiology between responders and non-responders. Follow-up assessments occur at 1, 6 and 12 months.

Study Protocol

Preparation

sessions

Dosing

2 sessions
90 min each

Integration

sessions

Study Arms & Interventions

Ketamine (Ketalar)

experimental

Target-controlled intravenous subanesthetic ketamine infusion up to 0.75 µg/ml for up to 90 minutes; step-wise increase unless new signs of consciousness.

Interventions

  • Ketamine0.75 µg/ml
    via IV• single infusion• 2 doses total

    TCI to target plasma concentration up to 0.75 µg/ml; infusion duration up to 90 minutes; two sessions 5 days apart

Placebo

inactive

Saline placebo infusion matched to active infusion schedule.

Interventions

  • Placebo
    via IV• single infusion• 2 doses total

    Saline solution, matched infusion schedule

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:\n\n* Clinically stable\n* Diagnosis of UWS or MCS based on repeated coma recovery scale-revised (CRS-R) or SECONDs\n* More than 28 days post-insult\n* Informed consent from the legal representative of the patient

Exclusion Criteria

  • Exclusion Criteria:\n\n* Neurological medications other than anti-spasticity drugs in the last 2 weeks or 4 half-lives\n* Previous neurological functional impairment other than related to their DoC\n* A history of psychotic disorders\n* Contraindication to MRI, EEG, PET or TMS\n* Use of nitrates or other vasodilators, central nervous system acting agents such as barbiturates, morphine and related drugs\n* Use of drugs known to interact with ketamine (e.g., strong CYP3A4 modulators, diazepam)\n* Coronary insufficiency\n* Other sympathomimetic drugs

Study Details

  • Status
    Recruiting
  • Phase
    Phase IIPhase III
  • Type
    interventional
  • Design
    Randomizedtriple Blind
  • Target Enrollment30 participants
  • Timeline
    Start: 2022-05-01
    End: 2026-05-01
  • Compounds
    KetaminePlacebo
  • Topic
    Neurological Injury

Locations

Centre Hospitalier Neurologique William Lennox — Ottignies-Louvain-la-Neuve, Wallonia, Belgium

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