Ketamine to Treat Patients With Post-comatose Disorders of Consciousness

NCT05343507 | Recruiting Phase 2

• 2 other identifiers: 2021_2112021-002321-23
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Disorder of Consciousness

Keywords

Psychedelics; Complexity; Ketamine; Clinical Diagnosis; Consciousness level

Outcome Measures

Primary Outcomes (2)

• New conscious behaviours

  New conscious behaviours (i.e., command following, visual pursuit) after the infusion of the ketamine as recorded via the "simplified evaluation of consciousness disorders" (SECONDs) behavioural scale, that are not seen before ketamine, during placebo infusion, or in baseline. The SECONDs has 8 items, with the most complex item linked to a higher conscious state. The score goes from 0 (coma) to 8 (emergent from the minimally conscious state).

  Max 90 minutes from Ketamine Infusion

• Higher brain complexity

  Higher brain complexity \[perturbational complexity index (PCI) or Lempel-Ziv complexity (LZC)\] during the infusion of ketamine. The investigators expect complexity to increase when new conscious behaviors are observed. If the patient does not show new signs of consciousness but has high complexity, the investigators expect to record memories of the experience in the follow-up phase. PCI and LZC values range from 0 (no complexity) to 1 (high complexity). The investigators expect complexity values to be proportional to the concentration of the drug.

  Max 90 minutes from Ketamine Infusion

Secondary Outcomes (3)

• PET biomarker

  From baseline

• MRI biomarker

  From baseline

• EEG power

  From baseline

Study Arms (2)

Ketalar arm

EXPERIMENTAL

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.

Drug: Ketalar 50 MG/ML Injectable Solution

Placebo arm

PLACEBO COMPARATOR

Patients will receive placebo (saline solution)

Drug: Placebo

Interventions

Ketalar 50 MG/ML Injectable Solution DRUG

Intravenous solution (other info already provided)

Also known as: Ketamine

Ketalar arm

Placebo DRUG

Saline Solution

Placebo arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Liege: lead
• Centre Hospitalier Universitaire de Liege: collaborator
• William Lennox Neurological Center UCLouvain: collaborator

Study Sites (1)

Centre Hospitalier Neurologique William Lennox

Ottignies-Louvain-la-Neuve, Wallonia, 1340, Belgium

RECRUITING

Related Publications (2)

• 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.

  PMID: 23946194 BACKGROUND

• 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.

  PMID: 31024740 BACKGROUND

MeSH Terms

Conditions

Consciousness Disorders

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Olivia Gosseries, PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paolo Cardone, MSc

CONTACT

0456309880; p.cardone@uliege.be

Charlotte Martial, PhD

CONTACT

cmartial@uliege.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: One investigator not involved in the data acquisition and analysis, and the pharmacist who will prepare the syringe for the TCI will not be blind.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Double-blind, placebo-controlled, cross-over RCT

Study Record Dates

• First Submitted: March 29, 2022
• First Posted: April 25, 2022
• Study Start: May 1, 2022
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2026
• Last Updated: November 7, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data will be shared with collaborators for the specified time allocated to each respective project. Whereas, data shared on the database will be anonymized and available indefinitely.
• Access Criteria: A written agreement between the groups (university or research teams)

Locations

BE (1)