Effectiveness of Music Therapy on Level of Consciousness

Study Overview
=================
Brief Summary
-----------------
It is known that even in patients with severe disorders of consciousness (DOC), the perception of known stimuli triggers emotional reactions that can be interpreted as an expression of a residual function of consciousness. Music therapy has a long tradition in neurological rehabilitation. Frequently, active therapies with own music making and singing are implemented in clinical settings. In DOC patients, it is more likely to use passive music listening. However, findings on effectiveness are limited, as only a few studies have systematically investigated the effects of music therapy in this population. Therefore, the investigators want to investigate the effectiveness of passive listening to preferred music on the level of consciousness.

Detailed Description
-----------------
Due to continuous improvements in acute medical care, the number of patients surviving severe brain damage has increased over the past decades. While some patients improve significantly during the first days after the injury, other patients remain in altered states of consciousness (i.e. coma, unresponsive wakefulness syndrome or minimally conscious state). In patients with disorders of consciousness (DOC), the auditory modality is preferably examined because the responsiveness within the motor and visual modality is often difficult to assess or impaired. Music is a special type of auditory stimulation that can be of particular benefit in DOC patients. The positive effects of music are attributed to the restoration of specific brain networks that are necessary for processing sensory inputs, as well as the emotional aspects of music, which can increase arousal and activate the reward system. Previous studies have shown that music, including passive listening to music, is associated with psychological and physical changes in both healthy and clinical populations. For example, listening to preferred music can reduce pain and anxiety and the need for sedation in different patient groups. Music therapy has a long tradition in neurological rehabilitation. In DOC patients, passive listening to music is used (in contrast to active therapies used in fully conscious patients). Efficacy results are inconsistent, however, since only a few studies have systematically investigated the effects of music therapy. In previous investigations, either the sample size is very small or no control conditions have been used. A study that met both quality criteria was published by Sun & Chen in 2015. The authors compared two groups: while the music group (n = 20) listened to their favorite music for 15 to 30 minutes three times a day for a period of four weeks, the control group received no stimulation. Although the GCS values increased significantly in both groups, the music group showed a significantly stronger improvement in the level of consciousness. Based on this study, the present study wants to compare the effectiveness of passive listening to music with two control conditions (alternative auditory stimulation and no auditory stimulation) in early neurological rehabilitation patients. It is a prospective, double-blind, controlled and randomized intervention study that is carried out monocentrically. Over a period of 24 months, 66 patients undergoing early neurological and neurosurgical rehabilitation after severe brain damage are included. For the individual patient, the study duration is a maximum of 38 days (preliminary phase: 3-7 days; intervention phase: 28 days; follow-up phase: 1-3 days). Patients are randomly assigned to one of three study arms (1. Musical stimulation; 2. Alternative auditory stimulation, 3. No auditory stimulation). In the preliminary phase (days 1 to 7), a native MRI (without contrast agent) and a CRS-R assessment are performed. In addition, there is a neurophysiological examination in which evoked potentials are recorded. In the subsequent main phase, the intervention takes place: Over a period of 28 days, the study participants wear headphones for 30 minutes a day, through which they are presented with preferred music (experimental arm), an audio book (comparative arm) or silence (control arm). In the main phase, a CRS-R test is carried out weekly to record the current state of consciousness. In the follow-up phase (1 to 3 days), the (native) MRI examination, the CRS-R assessment and the neurophysiological examination are repeated. The primary outcome measure is an improvement of the level of consciousness, measured with the Coma-Recovery-Scale-Revised (CRS-R).

Official Title
-----------------
Investigation of the Effectiveness of Music Therapy on the Level of Consciousness of Neurological Early Rehabilitation Patients

Conditions
-----------------
Neurologic Disorder, Traumatic Brain Injury, Disorder of Consciousness

Intervention / Treatment
-----------------
* Behavioral: Music Stimulation
* Behavioral: Alternative Stimulation
* Behavioral: No Auditory Stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: early neurological rehabilitation (phase B) traumatic brain injury disorder of consciousness (coma, UWS, MCS) at minimum two weeks after disease onset admission to intensive care unit written consent from the patient's legal representative Exclusion of pregnancy Exclusion Criteria: insufficient cardiorespiratory stability fractures or severe infratentorial brain injuries leading to impaired auditory evoked potentials previous brain damage Known mental disorders (dementia, depression) hearing loss or deafness in one or two ears wounds that do not allow you to wear headphones colonization with multi-resistant pathogens MRI contraindications claustrophobia weight>120 kg

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Music Stimulation<br>Patients preferred music is presented via headphones. | Behavioral: Music Stimulation<br>* Patients wear headphones for 30 minutes/day over a period of four weeks and listen to their preferred music.<br>|
| Active Comparator: Alternative Auditory Stimulation<br>An audio book is presented via headphones. | Behavioral: Alternative Stimulation<br>* Patients wear headphones for 30 minutes/day over a period of four weeks and listen to an audio book.<br>|
| Sham Comparator: No Auditory Stimulation<br>Silence is presented via headphones. | Behavioral: No Auditory Stimulation<br>* Patients wear headphones for 30 minutes/day over a period of four weeks and hear silence.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in level of consciousness | Level of consciousness is measured with the Coma-Recovery-Scale-Revised (Range: 0 to 23) before and after treatment. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in connectivity within the default mode network | Patients undergo a MRI scan before and after intervention. Each MRI scan has a duration of 30 minutes. Functional and structural sequences are measured. The resting-state scan (important for the assessment of the default mode network) has a duration of eight minutes and is performed without external stimulation. | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
neurological rehabilitation, music therapy, level of consciousness, default mode network