Disorders of consciousness as Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) after a coma due to acquired brain injury. Patients who emerged from the minimally conscious state (EMCS)
Conditions
Interventions
Trade Name: Ketalar
Product Name: Ketamine
Pharmaceutical Form: Infusion
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: Intravenous use
Sponsors
University of Liège
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - More than 18 years old - Clinically stable, not dependent on medical ventilators for respiration - Diagnosed as an unresponsive wakefulness syndrome, a minimally conscious state, or emergent from the minimally conscious state according to the international criteria and based on at least 2 standardized behavioral assessments with the Simplified Evaluation of CONsciousness Disorders (SECONDs) - More than 28 days post-insult - Informed consent from a legal representative of the patient Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Known allergy or hypersensitivity to ketamine - Active epilepsy (contrary advice by a neurologist upon standard EEG) - A history of previous neurological functional impairment other than related to their acquired brain injury - A history of psychotic disorders (schizophrenia or bipolar disorder) - Use of drugs known to interact with ketamine. Among them: thyroid hormones, diazepam and barbitudes, drugs that interact with CYP3A4, other anesthetic like tramadol or anestethic halogen - Patient with coronary insufficiency - Other sympathomimetic drugs - Conditional exclusion criteria: contraindication to MRI, PET, or TMS (e.g., electronic implanted devices, external ventricular drain). In case of those, the participant would be included only for the techniques without contradiction.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This clinical trial aims to evaluate the efficacy of intravenous ketamine for the treatment of patients with disorders of consciousness (DoC) after a coma and assess the prevalence of responders.;Secondary Objective: This study aims to also better characterize the phenotype of potential good candidates to ketamine treatment and identify a set of biomarkers that correlate with responsiveness (or non-responsiveness) to the therapy, as well to help underpinning the neural networks underlying the modulating action of ketamine on consciousness and brain complexity. ;Primary end point(s): Our main focus is on the link between consciousness and brain complexity. Thus, our primary endpoints are: 1. New signs of consciousness (e.g., response to command) measured by the SECONDs. 2. Brain complexity measured by LZC and/or PCI in the ketamine session at the highest dose, compared to placebo and the baseline. ;Timepoint(s) of evaluation of this end point: Two sessions separated by 5 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): We will investigate the additional index of SECONDs, baseline biomarkers of (behavior and brain) responders, and effects on spasticity. As such, our secondary endpoints are: 1. The “additional index” (from 0 to 100) of the SECONDs; 2. Baseline fMRI activity in the fronto-parietal network and the thalamo-cortical loop; 3. Baseline metabolic PET level in the fronto-parietal network and the thalamo-cortical loop; 4. EEG alpha connectivity measured via alpha centrality; 5. Spasticity measured via the Modified Ashworth Score; 6. Spasticity measured via EMG recording (H/M ratio); 7. Range of Motion.;Timepoint(s) of evaluation of this end point: Recording with EEG done from 20 minutes before giving ketamine to a maximum of 90 minutes after the reached concentration of blood ketamine. | — |
Countries
Belgium
Contacts
Public ContactComa Science Group
University of Liège
Outcome results
None listed