Effect of Intravenous Amantadine Sulphate on Disorders of Consciousness

Phase 2

Active, not recruiting

• Conditions: Electroencephalography; Consciousness Disorders; Amantadine
• Interventions: Drug: Amantadine Sulfate

• Registration Number: NCT06443827
• Lead Sponsor: Azienda Sanitaria dell'Alto Adige

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.

Study Timeline

• Study Start: 2018-09-15
• Primary Completion: 2024-01-10
• Study First Submitted: 2024-05-15
• Study First Submitted QC: 2024-05-30
• Status Verified: 2024-06
• Study First Posted: 2024-06-05
• Last Update Submitted: 2024-06-13
• Last Update Posted: 2024-06-14
• Study Completion: 2024-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 18

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
amantadine sulphate and placebo with schema A-B-A-B	Amantadine Sulfate	To obtain solid evidence of amantadine sulphate effects and their temporal dynamics, we conducted a 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).

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
"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

Trial Locations

Locations (1)

Hospital of Vipiteno; 🇮🇹 Vipiteno, Bolzano, Italy