Ketamine to treat patients with post-comatose disorders of consciousness
- Conditions
- Disorders of consciousness as Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) after a coma due to acquired brain injury.Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2021-002321-23-BE
- Lead Sponsor
- niversity of Liège
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 30
- 18-55 years old
- Clinically stable, not dependent on medical ventilators for respiration
- Diagnosed as an unresponsive wakefulness syndrome or a 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 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
- Use of neurological medications other than anti-spasticity drugs in the last 2 weeks or 4 half-lives of the drug
- A history of previous neurological functional impairment other than related to their acquired brain injury
- A history of psychiatric disorders
- First-degree psychiatric disorder in the family
- Contraindication to MRI, EEG, PET, or TMS (e.g., electronic implanted devices, external ventricular drain)
- Use of nitrates or other vasodilators, central nervous system acting agents such as barbiturates, morphine and related drugs
- Use of drugs known to interact with ketamine. Among them: thyroid hormones, diazepam, and barbiturates, drugs that interact with CYP3A4, other anesthetics like tramadol or anesthetic halogen
- Coronary insufficiency
- Kidney failure
- Other sympathomimetic drugs
- Active epilepsy
- Use of antiepileptic medication in the previous month
- Known allergy or hypersensitivity to ketamine
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 <br>good candidates to ketamine treatment and identify a set of <br>biomarkers that correlate with responsiveness (or non-responsiveness) <br>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): New signs of consciousness assessed via the Simplified Evaluation of CONsciousness Disorders (SECONDs) ;Timepoint(s) of evaluation of this end point: Two sessions separated by 5 days
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1-Change of complexity measured with Perturbation Complexity Index<br>2-Changes in EEG spectral power within fixed bands or dynamic <br>connectivity using median spectral connectivity and graph-theoretic <br>topology metrics<br>3-Changes in the probability of consciousness using a multivariate EEG <br>a classifier based on a machine-learning approach using 120 EEG markers.<br>4-Difference of PET, MRI, or EEG in the baseline assessment between responders and not-responders.;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.