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.
Details
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.