Apomorphine in Severe Brain-injured Patients (APODoC)
Disorder of Consciousness
About this trial
This is an interventional treatment trial for Disorder of Consciousness focused on measuring unresponsive wakefulness syndrome, minimally conscious state, apomorphine, treatment
Eligibility Criteria
Inclusion Criteria:
- 18-55 years old.
- Clinically stable, not dependent on medical ventilators for respiration.
- 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 6 weeks post-insult (starting the apomorphine treatment at 10 weeks minimum)
- No serious neurological impairments others than related to their acquired brain injury.
- No neurological medications other than anti-epileptic or anti-spasticity drugs within the last two weeks.
- No use of dopaminergic medications other than apomorphine within the last two weeks.
- Informed consent from legal representative of the patient (if patients recover, their consent will also be obtained).
Exclusion Criteria:
- 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 4 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)
- A 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).
- A history of previous neurological functional impairment.
- 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)
Sites / Locations
- University of Liege
- Hôpital Valdor - ISoSLRecruiting
- Centre Hospitalier Neurologique William LennoxRecruiting
- VITHAS
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Apomorphine
Isotonic saline
Apomorphine hydrochloride subcutaneous infusion 12 hours per day during 30 days: titration phase from 0 to 4 mg/h (5 days), maintenance phase at 4 mg/h, titration-maintenance phase with possible increase up to 6 mg/h depending on tolerance (18 days). Domperidone 20mg t.i.d per os (or via gastric tube) will be initiated to reduce common side effects 2 days before the initiation of apomorphine and maintained at least 7 days before an optional tapering off in the absence side effects.
Sodium chloride infusion following the administration procedure described for apomorphine