Effect of Intravenous Amantadine Sulphate on Disorders of Consciousness

NCT06443827 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 39049
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Amantadine; Consciousness Disorders; Electroencephalography

Keywords

DoC = Disorders of Consciousness; PSD = Power Spectral Density; Amantadine sulphate; EEG

Outcome Measures

Primary Outcomes (2)

• 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

• EEG band power alpha, beta, theta, delta

  Change in each canonical band power of EEG induced by amantadine sulphate

  days 14 and 28

Secondary Outcomes (1)

• "periodic" and "aperiodic" exponents of the average power spectral density

  days 14 and 28

Study Arms (1)

amantadine sulphate and placebo with schema A-B-A-B

EXPERIMENTAL

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).

Drug: Amantadine Sulfate

Interventions

Amantadine Sulfate DRUG

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

Also known as: physiological saline (0.9% NaCl solution)

amantadine sulphate and placebo with schema A-B-A-B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Sanitaria dell'Alto Adige: lead

Study Sites (1)

Hospital of Vipiteno

Sterzing, Bolzano, 39049, Italy

Location

MeSH Terms

Conditions

Consciousness Disorders

Interventions

Amantadine

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Viviana Versace, MD

  hospital of Vipiteno

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Blindness about treatment
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: 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).

Study Record Dates

• First Submitted: May 15, 2024
• First Posted: June 5, 2024
• Study Start: September 15, 2018
• Primary Completion: January 10, 2024
• Study Completion: September 30, 2024
• Last Updated: June 14, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)