Amantadine, Consciousness Disorders, Electroencephalography
Conditions
Keywords
DoC = Disorders of Consciousness, PSD = Power Spectral Density, Amantadine sulphate, EEG
Brief summary
Double-blind, placebo-controlled, crossover (within subjects) study with an A-B-A-B treatment scheme to investigate the neuromodulatory effects of intravenous amantadine sulphate at a single daily dose of 200 mg in patients with disorders of consciousness (unresponsive wakefulness syndrome and minimally conscious state) by integrating traditional neurobehavioral assessment with spectral analysis of electrocortical activity derived from 64-channel electroencephalography (EEG) recordings.
Detailed description
Research hypothesis Intravenous amantadine sulphate treatment (200 mg) over five days improves consciousness, defined as an increase in CRS-r score of at least 3 points, and changes the band powers of the EEG in patients with disorder of consciousness admitted in a Neurorehabilitation Department.
Interventions
intravenous amantadine sulphate at a single daily dose of 200 mg or physiological saline (0.9% NaCl solution)
Sponsors
Azienda Sanitaria dell'Alto Adige
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Blindness about treatment
Intervention model description
Double-blind, placebo-controlled, crossover (within subjects) study with an A-B-A-B treatment scheme, in which placebo (A) and amantadine sulphate (B) intervention sessions alternated weekly in the same patient for a total of four weeks (A1-B1-A2-B2).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Adults with disorders of consciousness due to acquired brain injury classified according to international guidelines based on CRS-R evaluation as unresponsive wakefulness syndrome/vegetative state (UWS/VS) or minimally conscious state (MCS) either in the subacute or chronic stage
Exclusion criteria
* Age \< 18 years * History of epileptic seizures/status epilepticus * Scalp defects * pregnancy * Severe uncompensated heart failure (NYHA IV) * Atrioventricular block (AV block) second-degree and third-degree * Known bradycardia (below 55 beats/minute) * Known long QT interval (QTc according to Bazett \> 420 ms * History of serious ventricular arrhythmias * Hypokalemia or hypomagnesemia * Impaired renal function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coma Recovery Scale-Revised (CRS-R) | days 14 and 28 | Increase in the Coma Recovery Scale-Revised (CRS-R) score of at least 1 point. The CRS-R consists of 23 items divided into six subscales designed to assess: Auditory (AU), Visual (V), Motor (M), Oromotor/Verbal (O), Communication (C), and Arousal functions (AR). The total score ranges between 0 (worst) and 23 (best). The subscales are composed of hierarchically ordered items; the lowest items (0) represent reflexive activity, while the highest items (4,5,6,3,2,3 points for AU, V, M, O, C respectively) represent cognitively mediated behaviours. We adopted a cut-off score of 8 for distinguish UWS/VS (\<8) from MCS (≥8) in patients induced by amantadine sulphate vs. placebo |
| EEG band power alpha, beta, theta, delta | days 14 and 28 | Change in each canonical band power of EEG induced by amantadine sulphate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| periodic and aperiodic exponents of the average power spectral density | days 14 and 28 | Change in periodic and aperiodic exponents of the average power spectral density vs. placebo and vs healthy controls |
Countries
Italy
Outcome results
None listed