Ketamine to Treat Patients With Post-comatose Disorders of Consciousness

NCT ID: NCT05343507

Last Updated: 2022-11-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-01
• Study Completion Date: 2026-05-01

Brief Summary

The investigators will run a Randomized Clinical Trial with 30 patients with disorders of consciousness (DoC), with intravenous subanesthetic doses of ketamine. Patients will simultaneously undergo TMS-EEG. The piloting will be done on 3 patients, with EEG only.

Detailed Description

The protocol will be organized in three phases: baseline, experimental, and follow-up. In the baseline, patients will receive a multimodal assessment [functional magnetic resonance imaging (fMRI), positron emission tomography (PET), electroencephalogram (EEG)]. The experimental phase is made of 2 sessions spaced 5 days apart: on day 1, patients will receive placebo (or ketamine), on day 5 patients will receive ketamine (or placebo). The order will be randomized and balanced. The investigators will use a targeted-controlled infusion (TCI) system to infuse a continuous subanesthetic dose of ketamine, which is known to have psychedelics effects, or a saline solution. The investigators will periodically assess for new signs of consciousness with the "simplified evaluation of consciousness disorders" (SECONDs) scale. The investigators will use transcranial magnetic stimulation coupled to EEG (TMS-EEG) to measure brain activity and calculate brain complexity. TMS-EEG will be performed from 20 minutes before the beginning of the infusion up to the max duration of the experiment (90 minutes). Another SECONDs will be performed on the following day of each session to control for carry-over effects. The primary outcomes are the emergence of new conscious behaviours and higher brain complexity following ketamine infusion. The secondary outcomes are baseline brain differences in neurophysiological and brain imaging measures between responders (new conscious behaviors or higher brain complexity) and non-responders (no new conscious behaviors or higher brain complexity). In the follow-up phase, patients' health will be evaluated at 1, 6, and 12 months.

Conditions

Disorder of Consciousness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Ketalar arm

Patients will receive ketamine (sold in the form of Ketalar) intravenously, up to 0.75 µg/ml concentration, for a maximum of 90' minutes. Ketalar concentration will be increased slowly in a step-wise manner unless new signs of consciousness are evident.

Group Type: EXPERIMENTAL

Ketalar 50 MG/ML Injectable Solution

Intervention Type: DRUG

Intravenous solution (other info already provided)

Placebo arm

Patients will receive placebo (saline solution)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Saline Solution

Interventions

Ketalar 50 MG/ML Injectable Solution

Intravenous solution (other info already provided)

Intervention Type: DRUG

Placebo

Saline Solution

Intervention Type: DRUG

Other Intervention Names

Ketamine

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• Neurological medications other than anti-spasticity drugs in the last 2 weeks or 4 half-lives
• Previous neurological functional impairment other than related to their DoC
• A history of psychotic disorders
• Contraindication to MRI, EEG, PET or TMS
• 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 (i.e., CYP3A4, diazepam, ...)
• Coronary insufficiency
• Other sympathomimetic drugs

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Liege

OTHER

Sponsor Role: collaborator

William Lennox Neurological Center UCLouvain

UNKNOWN

Sponsor Role: collaborator

University of Liege

OTHER

Sponsor Role: lead

Responsible Party

Olivia Gosseries

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Olivia Gosseries, PhD

Role: PRINCIPAL_INVESTIGATOR

Coma Science Group (ULiege) & Centre du Cerveau2 (CHU Liege)

Locations

Centre Hospitalier Neurologique William Lennox

Ottignies-Louvain-la-Neuve, Wallonia, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Paolo Cardone, MSc

Role: CONTACT

p.cardone@uliege.be

0456309880 ext. +32

Charlotte Martial, PhD

Role: CONTACT

cmartial@uliege.be

Facility Contacts

Paolo Cardone, M.Sc.

Role: primary

p.cardone@uliege.be

0456309880 ext. +32

Nicolas Lejeune, MD, PhD

Role: backup

Nicolas.Lejeune@uliege.be

References

Casali AG, Gosseries O, Rosanova M, Boly M, Sarasso S, Casali KR, Casarotto S, Bruno MA, Laureys S, Tononi G, Massimini M. A theoretically based index of consciousness independent of sensory processing and behavior. Sci Transl Med. 2013 Aug 14;5(198):198ra105. doi: 10.1126/scitranslmed.3006294.

Reference Type: BACKGROUND

PMID: 23946194 (View on PubMed)

Scott G, Carhart-Harris RL. Psychedelics as a treatment for disorders of consciousness. Neurosci Conscious. 2019 Apr 21;2019(1):niz003. doi: 10.1093/nc/niz003. eCollection 2019.

Reference Type: BACKGROUND

PMID: 31024740 (View on PubMed)

Other Identifiers

2021-002321-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2021_211

Identifier Type: -

Identifier Source: org_study_id