Disorders of consciousness
Conditions
Interventions
Trade Name: APO-go® PFS 5 mg/ml Solution for Infusion
Pharmaceutical Form: Solution for infusion in pre-filled syringe
INN or Proposed INN: Apomorphine Hydrochloride
CAS Number: 314-19-2
Other descrip
Sponsors
University of Liège
CHU Liège
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 18-80 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 - Informed consent from patient or legal representative of the patient. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 19
Exclusion criteria
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 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. - 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 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This clinical trial aims to clarify the prevalence of responders and the efficacy of apomorphine hydrochloride subcutaneous infusions for the treatment of patients with disorders of consciousness. ;Secondary Objective: This study aims to also better characterize the phenotype of potential good candidates to apomorphine treatment and identify a set of biomarkers that correlate with responsiveness (or non-responsiveness) to the therapy, as well as help underpin the neural networks underlying the modulating action of apomorphine on consciousness.;Primary end point(s): Change of diagnosis, total score and subscores from baseline in Coma Recovery Scale - Revised (CRS-R).;Timepoint(s) of evaluation of this end point: Once a week from inclusion until day 90. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1-Change of total score in Nociception Coma Scale - Revised (NCS-R). 2-Changes of total score in Disability Rating Scale (DRS). 3-Changes of total number of achieved items and highest achieved item in Wessex Head Injury Matrix (WHIM). 4-Change in circadian rhythmicity using actimetry. 5-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. 6-Changes in quantification of PET signal using standardized uptake values of fluorodeoxyglucose (SUV). 7-Changes in conventional EEG spectral power within fixed bands or dynamic connectivity using median spectral connectivity and graph-theoretic topology metrics 8-Change in the architecture of sleep cycles using 24h-EEG. 9-Changes in the probabilty of consciousness using a multivariate EEG classifier based on a machine-learning approach using 120 EEG markers. 10-Change of score in Glasgow Outcome Scale - Extended (GOS-E). 11-Change in diagnosis in Phone-adapted CRS-R.;Timepoint(s) of evaluation of this end point: 1-Once a week from inclusion until day 90. 2-Once a week from inclusion until day 90. 3-Once a week from inclusion until day 90. 4-Continuously from inclusion until day 90. 5-Before treatment initiation. 6-Before treatment initiation and after treatment completion. 7-Once a week from inclusion until day 90. 8-Before treatment initiation and after treatment completion. 9-Before treatment initiation and after treatment completion. 10-At 6 months, 12 months and 24 months after treatment initiation. 11-At 6 months, 12 months and 24 months after treatment initiation. | — |
Countries
Belgium
Contacts
Public ContactComa Science Group
University of Liège
Outcome results
None listed