Effect of Intravenous Amantadine Sulphate on Disorders of Consciousness

Electroencephalography Clinical Trial

— DOC-AMSUL  

Official title:

Effects of Intravenous Amantadine Sulphate on Brain Dynamics and Neurobehavioral Status in Patients With Disorders of Consciousness

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06443827
• Other study ID #: 39049
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 15, 2018
• Est. completion date: September 30, 2024

Study information

• Verified date: June 2024
• Source: Azienda Sanitaria dell'Alto Adige
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: September 30, 2024
• Est. primary completion date: January 10, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amantadine
• Consciousness Disorders
• Electroencephalography

Intervention

Drug:
• Amantadine Sulfate
intravenous amantadine sulphate at a single daily dose of 200 mg or physiological saline (0.9% NaCl solution)

Locations

Country	Name	City	State
Italy	Hospital of Vipiteno	Vipiteno	Bolzano

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Sanitaria dell'Alto Adige

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Coma Recovery Scale-Revised (CRS-R)	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	days 14 and 28
Primary	EEG band power alpha, beta, theta, delta	Change in each canonical band power of EEG induced by amantadine sulphate	days 14 and 28
Secondary	"periodic" and "aperiodic" exponents of the average power spectral density	Change in "periodic" and "aperiodic" exponents of the average power spectral density vs. placebo and vs healthy controls	days 14 and 28