NCT05213169 Apomorphine in Severe Brain-injured Patients
| NCT ID | NCT05213169 |
| Status | Recruiting |
| Phase | Phase 2, Phase 3 |
| Sponsor | University of Liege |
| Condition | Disorder of Consciousness |
| Study Type | INTERVENTIONAL |
| Enrollment | 48 participants |
| Start Date | 2021-06-18 |
| Primary Completion | 2026-12-31 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.
This trial targets 48 participants in total. It began in 2021-06-18 with a primary completion date of 2026-12-31.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
Background: Patients who survive severe brain injury may develop chronic disorders of consciousness (DoC). Treating these patients to improve recovery is extremely challenging because of scarce and inefficient therapeutical options. Among pharmacological treatments, apomorphine, a potent direct dopamine agonist, has exhibited promising behavioral effects, but its true efficacy and its mechanism remains unknown. This randomized controlled study aims to verify the effects of apomorphine subcutaneous infusion in patients with disorders of consciousness and investigate the neural networks targeted by this treatment. Methods/design: The double-blind randomized controlled trial will include 48 patients: 24 patients will be randomly assigned to the apomorphine and 24 to the placebo group. Investigators and the patients will be unaware of the nature of the treatment rendered. Primary outcome will be determined as behavioral response to treatment as measured by changes of diagnosis using the Coma Recovery Scale - Revised (CRS-R), while secondary outcome measures will include the Nociception Coma Scale - Revised (NCS-R), Disability Rating Scale (DRS), Wessex Head Injury Matrix (WHIM), circadian rhythm using actimetry, electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The Glasgow Outcome Scale - Extended (GOS-E) and a phone-adapted version of the CRS-R will be used for long-term follow-up. Statistical analyses will focus on the detection of changes induced by apomorphine treatment at the individual level (comparing data before and after treatment) and at the group level (comparing responders with non-responders). Response to treatment will be measured at four different levels: 1. behavioral response (CRS-R, NCS-R, DRS, WHIM, GOS-E, phone CRS-R), 2. brain metabolism (PET), 3. network connectivity (resting-state fMRI, clinical EEG and high-density EEG) and 4. Circadian rhythm changes (actimetry, body temperature, 24h-EEG). Discussion: Apomorphine is a promising and safe strategy for the treatment of DoC but efficacy, profile of the responding population and underlying mechanism remain to be determined. This trial will provide unprecedented data that will allow to investigate the response to apomorphine using multimodal methods and shed new light on the brain networks targeted by this drug in terms of behavioral response, functional connectivity and metabolism.
Eligibility 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 4 weeks post-insult. * 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)
Contact & Investigator
Olivia Gosseries, Ph.D.
PRINCIPAL INVESTIGATOR
University of Liege
Frequently Asked Questions
Who can join the NCT05213169 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, up to 80 Years, studying Disorder of Consciousness. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT05213169 trial and what does that mean for participants?
Phase 2 trials evaluate whether the treatment shows signs of effectiveness while continuing to monitor safety. More participants are enrolled than in Phase 1 to help refine the treatment protocol.
Is NCT05213169 currently recruiting?
Yes, NCT05213169 is actively recruiting participants. Contact the research team at emilie.szymkowicz@uliege.be for enrollment information.
Where is the NCT05213169 trial being conducted?
This trial is being conducted at Liège, Belgium, Liège, Belgium, Ottignies-Louvain-la-Neuve, Belgium, Valencia, Spain.
Who is sponsoring the NCT05213169 clinical trial?
NCT05213169 is sponsored by University of Liege. The principal investigator is Olivia Gosseries, Ph.D. at University of Liege. The trial plans to enroll 48 participants.