Can apomorphine and methylphenidate increase signs of consciousness in patients suffering with disorder of consciousness following severe brain injury?

Automated pupillometry and NIRS-EEG to detect signatures of consciousness in acute brain injury after apomorphine and methylphenidate stimulation: A placebo-controlled, randomized, cross-over study

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-001453-31-DK

Enrollment

Registered

2021-03-22

Start date

Unknown

Completion date

Unknown

Last updated

2021-10-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

We investigate the possible effects of commercially available apomorphine and methylphenidate on signatures of consciousness in patients admitted to the ICU with acute disorder of consciousness, using automated pupillometry and NIRS-EEG. MedDRA version: 20.0 Level: HLT Classification code 10013509 Term: Disturbances in consciousness NEC System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10067967 Term: Brain injury System Organ Class: 1002

Interventions

Trade Name: Methylphenidat Product Name: Methylphenidat Product Code: 29491 Pharmaceutical Form: Tablet INN or Proposed INN: METHYLPHENIDATE HYDROCHLORIDE CAS Number: 298-59-9 Concentration unit: mg m

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Age = 18 years. • Fluent in Danish or English language • Patients with severe acute traumatic or non-traumatic brain injury in a state of vegetative state/unresponsive wakefulness syndrome or minimal consciousness state according to FOUR and SECONDs. • Written informed consent for trial participation from next-of-kin. 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30

Exclusion criteria

Exclusion criteria: • Recovery of the ability to follow commands clinically prior to enrollment. • Pre-existing disorder of consciousness before the onset of brain injury. • Pre-existing mental or physical impairments. • Deafness, blindness or bilateral eye surgery before the onset of brain injury. • Ongoing use of dopamine agonists or antagonists within 6 half-lives of the drug. • Ongoing or previous use of psychoactive or psychotropic substances 2 weeks prior examination or within 6 half-lives of the drug. • Clinically unstable patients requiring immediate neurological, medical or surgical management. • Relatives' refusal of consent.

Design outcomes

Primary

Measure	Time frame
Main Objective: 1. To investigate, in a placebo-controlled, randomized, cross-over setting, the potential effects on pupillary function and neurovascular coupling with administrations of 20 mg methylphenidate in patients with acute disorder of consciousness 2. To investigate, in a placebo-controlled, randomized cross-over setting, the potential effects on pupillary function and neurovascular coupling with subcutaneous injections of 2 mg apomorphine in patients with acute disorder of consciousness;Secondary Objective: To assess, in a placebo-controlled setting, potential clinical effects on consciousness with administration of 20 mg methylphenidate and subcutaneous injection of 2 mg apomorphine, respectively, in patients with acute disorder of consciousness;Primary end point(s): 1. Significantly larger median pupillary size during passive and active paradigms compared to the immediate rest periods prior and after administration of methylphenidate and subcutane-ous apomorphine, as measured by automated pupillometer (for computational details, see Vassilieva et al. PeerJ 2019). 2. Neurovascular coupling (NIRS-EEG; see Figure 2) WCOH measures combined with EEG fea-tures from our machine learning algorithm (AMICA) following administration of maximum tolerated dose of methylphenidate and subcutaneous apomorphine (for computational details, see Othman et al. Neurocrit Care 2020).;Timepoint(s) of evaluation of this end point: Within 72 hours after confirmed consciousness diagnosis (vegetative state/unresponsive wakefulness syndrome or minimal consciousness state) provided the inclusion criteria are fulfilled and no exclusion criteria present.	—

Measure

Time frame

Main Objective: 1. To investigate, in a placebo-controlled, randomized, cross-over setting, the potential effects on pupillary function and neurovascular coupling with administrations of 20 mg methylphenidate in patients with acute disorder of consciousness 2. To investigate, in a placebo-controlled, randomized cross-over setting, the potential effects on pupillary function and neurovascular coupling with subcutaneous injections of 2 mg apomorphine in patients with acute disorder of consciousness;Secondary Objective: To assess, in a placebo-controlled setting, potential clinical effects on consciousness with administration of 20 mg methylphenidate and subcutaneous injection of 2 mg apomorphine, respectively, in patients with acute disorder of consciousness;Primary end point(s): 1. Significantly larger median pupillary size during passive and active paradigms compared to the immediate rest periods prior and after administration of methylphenidate and subcutane-ous apomorphine, as measured by automated pupillometer (for computational details, see Vassilieva et al. PeerJ 2019). 2. Neurovascular coupling (NIRS-EEG; see Figure 2) WCOH measures combined with EEG fea-tures from our machine learning algorithm (AMICA) following administration of maximum tolerated dose of methylphenidate and subcutaneous apomorphine (for computational details, see Othman et al. Neurocrit Care 2020).;Timepoint(s) of evaluation of this end point: Within 72 hours after confirmed consciousness diagnosis (vegetative state/unresponsive wakefulness syndrome or minimal consciousness state) provided the inclusion criteria are fulfilled and no exclusion criteria present.

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Secondary

Measure	Time frame
Secondary end point(s): 1. Improvement of conscious state after administration of pharmacological stimulating therapies, with maximum tolerated doses of methylphenidate and subcutaneous apomorphine, as measured by FOUR and SECONDs scores.;Timepoint(s) of evaluation of this end point: Within 72 hours after confirmed consciousness diagnosis (vegetative state/unresponsive wakefulness syndrome or minimal consciousness state) provided the inclusion criteria are fulfilled and no exclusion criteria present.	—

Measure

Time frame

Secondary end point(s): 1. Improvement of conscious state after administration of pharmacological stimulating therapies, with maximum tolerated doses of methylphenidate and subcutaneous apomorphine, as measured by FOUR and SECONDs scores.;Timepoint(s) of evaluation of this end point: Within 72 hours after confirmed consciousness diagnosis (vegetative state/unresponsive wakefulness syndrome or minimal consciousness state) provided the inclusion criteria are fulfilled and no exclusion criteria present.

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Countries

Denmark

Contacts

Public ContactDepartment of Neurology

Copenhagen University Hospital Rigshospitalet

daniel.kondziella@regionh.dk004535456368

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026