Ketamine to treat patients with post-comatose disorders of consciousness

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universite De Liege, Centre Hospitalier Universitaire De Liege

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

1 Jan 2022 → ongoing

Decision date (initial)

2024-10-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Fonds de la Recherche Scientifique – FNRS · Fonds Léon Fredericq · University of Liege

External identifiers

EU CT number

2024-518433-29-00

EudraCT number

2021-002321-23

ClinicalTrials.gov

NCT05343507

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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 objectives 1

1. Characters: 356/1000 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.

Conditions and MedDRA coding

Disorder of Consciousness, severe brain injury

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. More than 18 years old
2. Clinically stable, not dependent on medical ventilators for respiration
3. 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)
4. More than 28 days post-insult
5. Informed consent from a legal representative of the patient

Exclusion criteria 9

1. Known allergy or hypersensitivity to ketamine
2. Active epilepsy (contrary advice by a neurologist upon standard EEG)
3. A history of previous neurological functional impairment other than related to their acquired brain injury
4. A history of psychotic disorders (schizophrenia or bipolar disorder)
5. 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
6. Patient with coronary insufficiency
7. Other sympathomimetic drugs
8. Pregnancy
9. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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.

Secondary endpoints 7

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universite De Liege

Sponsor organisation

Universite De Liege

Address

Ba1, Place Du Vingt-Aout 7 Place Du Vingt-Aout 7

City

Liege

Postcode

4000

Country

Belgium

Scientific contact point

Organisation

Universite De Liege

Contact name

Olivia Gosseries

Public contact point

Organisation

Universite De Liege

Contact name

Olivia Gosseries

Centre Hospitalier Universitaire De Liege

Sponsor organisation

Centre Hospitalier Universitaire De Liege

Address

Avenue De L'hopital 1

City

Liege

Postcode

4000

Country

Belgium

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Liege

Contact name

Vincent Bonhomme

Public contact point

Organisation

Centre Hospitalier Universitaire De Liege

Contact name

Vincent Bonhomme

Sponsor responsibilities

Article 77 compliance

Universite De Liege

Contact point sponsor

Universite De Liege

Article 77 implementation

Universite De Liege

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications