Apomorphine hydrochloride hemihydrate for Disorder of consciousness | Severe brain injury

Inclusion criteria

• {"criterion_text":"- 18-70 years old, cinically stable, diagnosed as in an unresponsive wakefulness syndrome or minimally conscious state according to the international criteria and based on at least 2 consistent CRS-R in the last 14 days (one CRS-R in the last 7 days), more than 4 weeks post-insult, informed consent from patient or legal representative of the patient."}

Exclusion criteria

• {"criterion_text":"- Use of dopamine agonists or antagonists (e.g. amantadine, bromocriptine, l-dopa, pramipexole, ropinirole, amphetamine, bupropion, methylphenidate / risperidone, haloperidol, chlorpromazine, flupentixol, clozapine, olanzapine, quetiapine) in the last 2 weeks or 4 half-lives of the drug; use of neurological medications other than anti-epileptic or anti-spasticity drugs in the last 2 weeks or 4 half-lives of the drug; use of drugs with known significant prolongation of the QT interval (e.g. class 1 antiarrythmics, sotalol, macrolides, quinolones, antipsychotic drugs, tricyclic antidepressants, methadone, chloroquine, quinine) in the last 2 weeks or 4 half-lives of the drug; corrected QT interval over 480ms (calculated using Bazett’s formula on a standard 12-lead ECG recorded in the last 14 days) or other risk factors for arrhythmia (congestive cardiac failure, severe hepatic impairment or significant electrolyte disturbance); history of previous neurological functional impairment other than related to their acquired brain injury; contraindication to MRI, EEG, or PET (e.g., electronic implanted devices, active epilepsy, external ventricular drain); use of nitrates or other vasodilators, central nervous system acting agents such as barbiturates, morphine and related drugs (relative exclusion criterion)."}

Primary endpoints

• {"endpoint_text":"- Change of diagnosis from baseline in Coma Recovery Scale - Revised (CRS-R)","definition_or_measurement_approach":"Measured as change in diagnosis from baseline using the Coma Recovery Scale - Revised (CRS-R)."}

Secondary endpoints

• {"endpoint_text":"- Change of total score in Nociception Coma Scale - Revised (NCS-R)","definition_or_measurement_approach":"Measured as change in total score of the Nociception Coma Scale - Revised (NCS-R)."}
• {"endpoint_text":"- Changes in EEG spectral power within fixed bands or dynamic connectivity using median spectral connectivity and graph-theoretic topology metrics","definition_or_measurement_approach":"Measured by EEG spectral power within fixed frequency bands and dynamic connectivity using median spectral connectivity and graph-theoretic topology metrics."}
• {"endpoint_text":"- Changes in the probabilty of consciousness using a multivariate EEG classifier based on a machine-learning approach using 120 EEG markers","definition_or_measurement_approach":"Measured by a multivariate EEG classifier (machine-learning) using 120 EEG markers to estimate probability of consciousness."}
• {"endpoint_text":"- Changes in quantification of PET signal using standardized uptake values of fluorodeoxyglucose","definition_or_measurement_approach":"Measured by changes in PET standardized uptake values (FDG)."}
• {"endpoint_text":"- Changes in MRI functional connectivity using a seed-voxel approach, between regions of interest (here: striatum, globus pallidus interna, thalamus and prefrontal cortex) and the time course from all other brain voxels","definition_or_measurement_approach":"Measured by MRI functional connectivity using a seed-voxel approach between listed ROIs and all other brain voxels."}
• {"endpoint_text":"- Change in circadian rhythmicity using actimetry and body temperature variations","definition_or_measurement_approach":"Measured via actimetry and body temperature variations to assess circadian rhythmicity."}
• {"endpoint_text":"- Change in the architecture of sleep cycles using night EEG","definition_or_measurement_approach":"Measured by night EEG to assess changes in sleep cycle architecture."}
• {"endpoint_text":"- Change of score in Glasgow Outcome Scale - Extended (GOS-E)","definition_or_measurement_approach":"Measured as change in Glasgow Outcome Scale - Extended (GOS-E) score."}
• {"endpoint_text":"- Change in diagnosis in Phone-adapted CRS-R","definition_or_measurement_approach":"Measured as change in diagnosis using a phone-adapted version of the CRS-R."}

Belgium

Earliest CTIS Part Ii Submission Date

14-09-2024

Latest Decision Or Authorization Date

10-02-2025

Processing Time Days

149

Number Of Sites

3

Number Of Participants

54

Spain

Earliest CTIS Part Ii Submission Date

11-07-2025

Latest Decision Or Authorization Date

24-07-2025

Processing Time Days

13

Number Of Sites

3

Number Of Participants

48

Primary sponsor

Full Name

Universite De Liege

Organisation Type

Educational Institution

Country Of Registered Address

Belgium

Third parties

• {"country":"","full_name":"Britannia Pharmaceuticals Limited","duties_or_roles":"Monetary support","organisation_type":""}

Co-sponsors

• CHU De Liege