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Disorder of ConsciousnessPhase 2/3NCT05343507

Ketamine to Treat Patients With Post-comatose Disorders of Consciousness

A Phase 2/3 study testing Ketalar 50 MG/ML Injectable Solution in people with Disorder of Consciousness, run by University of Liege at 1 site in Belgium.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Disorder of Consciousness
What is being tested?
Ketalar 50 MG/ML Injectable Solution
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteBelgium
Study dates
1 May 2022to 1 May 2026
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Paolo Cardone, MSc contact

0456309880 ext. +32

p.cardone@uliege.be

Charlotte Martial, PhD contact

cmartial@uliege.be

Belgium1 site, 1 recruiting

  • Centre Hospitalier Neurologique William Lennox

    Ottignies-Louvain-la-Neuve, Wallonia, 1340

    Paolo Cardone, M.Sc., 0456309880 ext. +32, p.cardone@uliege.be

    Nicolas Lejeune, MD, PhD, Nicolas.Lejeune@uliege.be

    Recruiting

Other trials in Belgium

About this study

Official title: Complexity-enhancing Drugs to Treat Disorders of Consciousness (DoC): a Ketamine Study

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.

Read the 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.

Being tested
Ketalar 50 MG/ML Injectable Solution, Placebo
Keywords
Psychedelics, Complexity, Ketamine, Clinical Diagnosis, Consciousness level
Medical subject headings
Consciousness Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ketalar 50 MG/ML Injectable SolutionDrug

    Also called Ketamine

    Intravenous solution (other info already provided)

  • PlaceboDrug

    Saline Solution

Study groups in NCT05343507
Study groupRoleWhat they receive
Ketalar armExperimentalPatients 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.
Receives: Drug: Ketalar 50 MG/ML Injectable Solution
Placebo armPlacebo comparatorPatients will receive placebo (saline solution)
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Max 90 minutes from Ketamine Infusion

  2. 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.

    Measured: Max 90 minutes from Ketamine Infusion

Secondary outcomes (3)

  1. PET biomarker

    Different baseline PET signal between responders (patients who show new signs of consciousness or higher brain complexity after the drug), and non-responders (who do not show new signs of consciousness or higher brain complexity). In particular, higher metabolism [measured by standardized uptake value (SUV)] in responders compared to non-responders.

    Measured: From baseline

  2. MRI biomarker

    Different baseline MRI between responders (patients who show new signs of consciousness or higher brain complexity after the drug), and non-responders (who do not show new signs of consciousness or higher brain complexity). In particular, higher resting-state BOLD activity in responders compared to non-responders and more preserved brain structures.

    Measured: From baseline

  3. EEG power

    Different baseline EEG signal between responders (patients who show new signs of consciousness or higher brain complexity after the drug), and non-responders (who do not show new signs of consciousness or higher brain complexity). In particular, higher alpha-band activity in responders compared to non-responders.

    Measured: From baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2022
  2. Study start1 May 2022
  3. Primary completion1 May 2025 (estimated)
  4. Study completion1 May 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
Double-blind, placebo-controlled, cross-over RCT
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05343507
Sponsor's protocol ID
2021_211
Other IDs
2021-002321-23
Status last verified
Nov 2022
First submitted
29 Mar 2022
Last updated
7 Nov 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data will be anonymized and shared among collaborators upon reasonable request and agreement. If possible, data will be shared in an open-access database to ensure the values of open science.

Publications

  • 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.

    PubMed 23946194

  • 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.

    PubMed 31024740

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Ketalar 50 MG/ML Injectable Solution in people with Disorder of Consciousness, run by University of Liege at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 7 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Paolo Cardone, MSc (0456309880 ext. +32, p.cardone@uliege.be), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

New conscious behaviours (time frame: Max 90 minutes from Ketamine Infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05343507, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2022.

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