Treating severe brain-injured patients with apomorphine

Phase 1

• Conditions: Disorders of consciousness; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2018-003144-23-BE
• Lead Sponsor: niversity of Liège

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-08-09
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 54

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

- 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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.<br>;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.