Music Intervention and Transcranial Electrical Stimulation for Neurological Diseases

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trial is to evaluate the efficacy of a musical interventionand non-invasive brain stimulation in neurological patients. The main questions it aims to answer are: to evaluate the residual neuroplastic processes in DOC state related to music exposure to determine the putative modulation of the aforementioned processes and the clinical outcome of DOC patients by non-pharmacological strategies, i.e., electric (tDCS) and music stimulation to evaluate the impact of this intervention on caregiver's burden and psychological distress. Participants will be randomly assigned to one of three different music-listening intervention groups. Primary outcomes will be clinical, that is based on the neurologist's observations of clinical improvement, and neurophysiological, collected pre-intervention, post-intervention and post-placebo.

Official Title
-----------------
Music Intervention and Transcranial Electrical Stimulation for Treating Neurological Diseases

Conditions
-----------------
Stroke, Disorder of Consciousness

Intervention / Treatment
-----------------
* Other: Combinatory effect of music stimulation and neurostimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years Post-stroke aphasia Post-stroke neglect Patients with disorders of consciusness (DOC) Exclusion Criteria: No auditory injury no hystory of neurological disease No hystory of psychiatric disease Previous stroke use of alcohol and drugs premorbid dementia

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Three groups of neurological patients will be considered for the study. For each group, participants will be randomly allocated to one of three intervention groups. These interventions will consist of a combination of musical stimulation, sham stimulation, tDCS and noise.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Group 1 will receive tEs combined with music stimulation for 2 weeks, 1 week of wash out, then sham stimulation combined with noise (placebo) for other 2 weeks. | Other: Combinatory effect of music stimulation and neurostimulation<br>* music<br>|
| Experimental: Group 2<br>Group 2 will receive sham stimulation and noise (placebo) for the first 2 weeks, then 1 week wash out, and finally tEs and music stimulation for other 2 weeks. | Other: Combinatory effect of music stimulation and neurostimulation<br>* music<br>|
| Experimental: Group 3<br>Group 3 will receive only music stimulation and sham stimulation for 2 weeks, 1 week of wash out, then sham stimulation and noise (placebo) for another 2 weeks. | Other: Combinatory effect of music stimulation and neurostimulation<br>* music<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychological outcomes | -Coma Recovery Scale-Revised (CRS-R) - (0-23). High score means a better outcome. | Change from baseline Coma Recovery Scale- Revised at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Disability Rating Scale (DRS) - (0-29). High score means a worse outcome. | Change from baseline Disability Rating Scale at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Rancho Levels of Cognitive Functioning (LCF) - (1-8). High score means a better outcome. | Change from baseline Rancho Levels of Cognitive Functioning at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Glasgow Outcome Scale- Extended (GOS-E) - (1-8). High score means a better outcome. | Change from baseline Glasgow Outcome Scale- Extended at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Aachener Aphasie Test (AAT). This test includes six subtests: spontaneous speech, token test, repetition, written language, naming, and comprehension. Spontaneous speech is structured in six parts (0-30). High score means a better performance; Token test is composed by 50 items; for the score the number of error id considered (0-50). Repetition sub test is composed by 50 items; for each item the score range from 0 to 3; high score means better outcome (0-150). Written language subtest is composed by 30 items; for each item the score range from 0 to 3; high score means better outcome (0-90). Naming subtest is composed by 40 items; for each item the score range from 0 to 3; high score means better outcome (0-120). Comprehension subtest is composed by 40 items; for each item the score range from 0 to 3; high score means better outcome (0-120). | Change from baseline Aachener Aphasie Test at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Italian version of Functional Outcome Questionnaire for Aphasie (FOQ-A) - (32-160). High score means a better outcome. | Change from baseline Italian version of Functional Outcome Questionnaire for Aphasie at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Functional Assessment Measure - Cognitive subscale - (FAM) - (14-98); high score means a better outcome. | Change from baseline Functional Assessment Measure - Cognitive subscale at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Quality of Life questionnaire for Aphasics (QLQA) - (0-148); High score means a better outcome. | Change from baseline Quality of Life Questionnaire for aphasics at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | The semi-structured scale for functional evaluation of personal neglect - (0-9); High score means a worse outcome. | Change from baseline The semi-structured scale for functional evaluation of personal neglect at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Barrage test (0-36). High score means a better outcome. | Change from baseline Barrage Test at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Letter cancellation test - (0-104). High score means a better outcome. | Change from baseline Letter cancellation test at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Sentence reading test (0-6). High score means a worse outcome. | Change from baseline Sentence reading test at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | Wundt-Jastrow area illusion test (0-20). High score means a worse outcome. | Change from baseline Wundt-Jastrow area illusion test at 2 weeks and 4 weeks | 
| Neuropsychological outcomes | The semi structured scale for the functional evaluation of extrapersonal neglect (0-9). High score means a worse outcome. | Change from baseline The semi structured scale for the functional evaluation of extrapersonal neglect at 2 weeks and 4 weeks | 
| Neurophysiological outcome | The ratio of fast (8-30 Hz, α-β) to slow (2-8 Hz, δ-θ) oscillation amplitude at the midline electrodes (Fz, Cz, Pz, Oz) will be measured and compared pre- and post intervention. | Change from baseline oscillation at 2 weeks and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Caregiver psychological distress | Back depression Inventory II (BDI II) - (0-63). High score means a worse outcome. | Change from baseline Back depression Inventory II at 2 weeks and 4 weeks | 
| Caregiver psychological distress | State-trait anxiety inventory (STAI-Y). It is composed by two scales: STAI-Y State (20-80) and STAI-Y Trait (20-80). High score means a worse outcome. | Change from baseline State-trait anxiety inventory; at 2 weeks and 4 weeks | 
| Caregiver psychological distress | Psychophysiological Questionnaire (30-120). WHOQOL-BREF. | Change from baseline Questionario psicofisiologico (CBA) at 2 weeks and 4 weeks | 
| Caregiver psychological distress | Prolonged grief disorder -12 (PG-12) - (11-55). High score means a worse outcome. | Change from baseline Prolonged grief disorder -12 at 2 weeks and 4 weeks | 
| Caregiver psychological distress | Family strain questionnaire (FSQ) - (1-44). High score means a worse outcome. | Change from baseline Family strain questionnaire at 2 weeks and 4 weeks | 
| Caregiver psychological distress | better outcome. | Change from baseline Wolrd health organization - quality of life at 2 weeks and 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
music stimulation, tDCS, Aphasia, Neglect, DOC, Stroke