<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04442971</url>
  </required_header>
  <id_info>
    <org_study_id>DOC-MT</org_study_id>
    <nct_id>NCT04442971</nct_id>
  </id_info>
  <brief_title>Effectiveness of Music Therapy on Level of Consciousness</brief_title>
  <official_title>Investigation of the Effectiveness of Music Therapy on the Level of Consciousness of Neurological Early Rehabilitation Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BDH-Klinik Hessisch Oldendorf</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BDH-Klinik Hessisch Oldendorf</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is known that even in patients with severe disorders of consciousness (DOC), the&#xD;
      perception of known stimuli triggers emotional reactions that can be interpreted as an&#xD;
      expression of a residual function of consciousness. Music therapy has a long tradition in&#xD;
      neurological rehabilitation. Frequently, active therapies with own music making and singing&#xD;
      are implemented in clinical settings. In DOC patients, it is more likely to use passive music&#xD;
      listening. However, findings on effectiveness are limited, as only a few studies have&#xD;
      systematically investigated the effects of music therapy in this population. Therefore, the&#xD;
      investigators want to investigate the effectiveness of passive listening to preferred music&#xD;
      on the level of consciousness.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Due to continuous improvements in acute medical care, the number of patients surviving severe&#xD;
      brain damage has increased over the past decades. While some patients improve significantly&#xD;
      during the first days after the injury, other patients remain in altered states of&#xD;
      consciousness (i.e. coma, unresponsive wakefulness syndrome or minimally conscious state). In&#xD;
      patients with disorders of consciousness (DOC), the auditory modality is preferably examined&#xD;
      because the responsiveness within the motor and visual modality is often difficult to assess&#xD;
      or impaired. Music is a special type of auditory stimulation that can be of particular&#xD;
      benefit in DOC patients. The positive effects of music are attributed to the restoration of&#xD;
      specific brain networks that are necessary for processing sensory inputs, as well as the&#xD;
      emotional aspects of music, which can increase arousal and activate the reward system.&#xD;
      Previous studies have shown that music, including passive listening to music, is associated&#xD;
      with psychological and physical changes in both healthy and clinical populations. For&#xD;
      example, listening to preferred music can reduce pain and anxiety and the need for sedation&#xD;
      in different patient groups.&#xD;
&#xD;
      Music therapy has a long tradition in neurological rehabilitation. In DOC patients, passive&#xD;
      listening to music is used (in contrast to active therapies used in fully conscious&#xD;
      patients). Efficacy results are inconsistent, however, since only a few studies have&#xD;
      systematically investigated the effects of music therapy. In previous investigations, either&#xD;
      the sample size is very small or no control conditions have been used. A study that met both&#xD;
      quality criteria was published by Sun &amp; Chen in 2015. The authors compared two groups: while&#xD;
      the music group (n = 20) listened to their favorite music for 15 to 30 minutes three times a&#xD;
      day for a period of four weeks, the control group received no stimulation. Although the GCS&#xD;
      values increased significantly in both groups, the music group showed a significantly&#xD;
      stronger improvement in the level of consciousness. Based on this study, the present study&#xD;
      wants to compare the effectiveness of passive listening to music with two control conditions&#xD;
      (alternative auditory stimulation and no auditory stimulation) in early neurological&#xD;
      rehabilitation patients.&#xD;
&#xD;
      It is a prospective, double-blind, controlled and randomized intervention study that is&#xD;
      carried out monocentrically. Over a period of 24 months, 66 patients undergoing early&#xD;
      neurological and neurosurgical rehabilitation after severe brain damage are included. For the&#xD;
      individual patient, the study duration is a maximum of 38 days (preliminary phase: 3-7 days;&#xD;
      intervention phase: 28 days; follow-up phase: 1-3 days). Patients are randomly assigned to&#xD;
      one of three study arms (1. Musical stimulation; 2. Alternative auditory stimulation, 3. No&#xD;
      auditory stimulation). In the preliminary phase (days 1 to 7), a native MRI (without contrast&#xD;
      agent) and a CRS-R assessment are performed. In addition, there is a neurophysiological&#xD;
      examination in which evoked potentials are recorded. In the subsequent main phase, the&#xD;
      intervention takes place: Over a period of 28 days, the study participants wear headphones&#xD;
      for 30 minutes a day, through which they are presented with preferred music (experimental&#xD;
      arm), an audio book (comparative arm) or silence (control arm). In the main phase, a CRS-R&#xD;
      test is carried out weekly to record the current state of consciousness. In the follow-up&#xD;
      phase (1 to 3 days), the (native) MRI examination, the CRS-R assessment and the&#xD;
      neurophysiological examination are repeated. The primary outcome measure is an improvement of&#xD;
      the level of consciousness, measured with the Coma-Recovery-Scale-Revised (CRS-R).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">December 15, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 15, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in level of consciousness</measure>
    <time_frame>4 weeks</time_frame>
    <description>Level of consciousness is measured with the Coma-Recovery-Scale-Revised (Range: 0 to 23) before and after treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in connectivity within the default mode network</measure>
    <time_frame>4 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">66</enrollment>
  <condition>Neurologic Disorder</condition>
  <condition>Traumatic Brain Injury</condition>
  <condition>Disorder of Consciousness</condition>
  <arm_group>
    <arm_group_label>Music Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients preferred music is presented via headphones.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alternative Auditory Stimulation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>An audio book is presented via headphones.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Auditory Stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Silence is presented via headphones.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Music Stimulation</intervention_name>
    <description>Patients wear headphones for 30 minutes/day over a period of four weeks and listen to their preferred music.</description>
    <arm_group_label>Music Stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Alternative Stimulation</intervention_name>
    <description>Patients wear headphones for 30 minutes/day over a period of four weeks and listen to an audio book.</description>
    <arm_group_label>Alternative Auditory Stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>No Auditory Stimulation</intervention_name>
    <description>Patients wear headphones for 30 minutes/day over a period of four weeks and hear silence.</description>
    <arm_group_label>No Auditory Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  early neurological rehabilitation (phase B)&#xD;
&#xD;
          -  traumatic brain injury&#xD;
&#xD;
          -  disorder of consciousness (coma, UWS, MCS)&#xD;
&#xD;
          -  at minimum two weeks after disease onset&#xD;
&#xD;
          -  admission to intensive care unit&#xD;
&#xD;
          -  written consent from the patient's legal representative&#xD;
&#xD;
          -  Exclusion of pregnancy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  insufficient cardiorespiratory stability&#xD;
&#xD;
          -  fractures or severe infratentorial brain injuries leading to impaired auditory evoked&#xD;
             potentials&#xD;
&#xD;
          -  previous brain damage&#xD;
&#xD;
          -  Known mental disorders (dementia, depression)&#xD;
&#xD;
          -  hearing loss or deafness in one or two ears&#xD;
&#xD;
          -  wounds that do not allow you to wear headphones&#xD;
&#xD;
          -  colonization with multi-resistant pathogens&#xD;
&#xD;
          -  MRI contraindications&#xD;
&#xD;
          -  claustrophobia&#xD;
&#xD;
          -  weight&gt;120 kg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jens D Rollnik, MD</last_name>
    <role>Study Director</role>
    <affiliation>BDH-Clinic Hessisch Oldendorf</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Melanie Boltzmann, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>BDH-Clinic Hessisch Oldendorf</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Melanie Boltzmann, PhD</last_name>
    <phone>0049 5152 781 256</phone>
    <email>m.boltzmann@bdh-klinik-hessisch.oldendorf</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Simone B Schmidt, PhD</last_name>
    <phone>0049 5152 781 215</phone>
    <email>si.schmidt@bdh-klinik-hessisch.oldendorf</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>BDH-Clinic Hessisch Oldendorf</name>
      <address>
        <city>Hessisch Oldendorf</city>
        <zip>31840</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melanie Boltzmann, PhD</last_name>
      <phone>0049 5152 781 256</phone>
      <email>m.boltzmann@bdh-klinik-hessisch-oldendorf.de</email>
    </contact>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Kotchoubey B, Pavlov YG, Kleber B. Music in Research and Rehabilitation of Disorders of Consciousness: Psychological and Neurophysiological Foundations. Front Psychol. 2015 Nov 27;6:1763. doi: 10.3389/fpsyg.2015.01763. eCollection 2015.</citation>
    <PMID>26640445</PMID>
  </reference>
  <reference>
    <citation>Perrin F, Castro M, Tillmann B, Luaute J. Promoting the use of personally relevant stimuli for investigating patients with disorders of consciousness. Front Psychol. 2015 Jul 30;6:1102. doi: 10.3389/fpsyg.2015.01102. eCollection 2015.</citation>
    <PMID>26284020</PMID>
  </reference>
  <reference>
    <citation>Hole J, Hirsch M, Ball E, Meads C. Music as an aid for postoperative recovery in adults: a systematic review and meta-analysis. Lancet. 2015 Oct 24;386(10004):1659-71. doi: 10.1016/S0140-6736(15)60169-6. Epub 2015 Aug 12. Erratum In: Lancet. 2015 Oct 24;386(10004):1630.</citation>
    <PMID>26277246</PMID>
  </reference>
  <reference>
    <citation>Chlan LL, Weinert CR, Heiderscheit A, Tracy MF, Skaar DJ, Guttormson JL, Savik K. Effects of patient-directed music intervention on anxiety and sedative exposure in critically ill patients receiving mechanical ventilatory support: a randomized clinical trial. JAMA. 2013 Jun 12;309(22):2335-44. doi: 10.1001/jama.2013.5670.</citation>
    <PMID>23689789</PMID>
  </reference>
  <reference>
    <citation>Sun J, Chen W. Music therapy for coma patients: preliminary results. Eur Rev Med Pharmacol Sci. 2015 Apr;19(7):1209-18.</citation>
    <PMID>25912580</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>July 26, 2023</last_update_submitted>
  <last_update_submitted_qc>July 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>neurological rehabilitation</keyword>
  <keyword>music therapy</keyword>
  <keyword>level of consciousness</keyword>
  <keyword>default mode network</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Consciousness Disorders</mesh_term>
    <mesh_term>Nervous System Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD that underlie results in a publication.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Period of availability begins when results are published, at the earliest in Dec 2022</ipd_time_frame>
    <ipd_access_criteria>IPD can be obtained from the principal investigator upon reasonable request.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04442971
org study id: DOC-MT
nct id: NCT04442971
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in level of consciousness
time frame: 4 weeks
description: Level of consciousness is measured with the Coma-Recovery-Scale-Revised (Range: 0 to 23) before and after treatment.
measure: Change in connectivity within the default mode network
time frame: 4 weeks
description: 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.
arm group label: Music Stimulation
arm group type: Experimental
description: Patients preferred music is presented via headphones.
arm group label: Alternative Auditory Stimulation
arm group type: Active Comparator
description: An audio book is presented via headphones.
arm group label: No Auditory Stimulation
arm group type: Sham Comparator
description: Silence is presented via headphones.
intervention type: Behavioral
intervention name: Music Stimulation
description: Patients wear headphones for 30 minutes/day over a period of four weeks and listen to their preferred music.
arm group label: Music Stimulation
intervention type: Behavioral
intervention name: Alternative Stimulation
description: Patients wear headphones for 30 minutes/day over a period of four weeks and listen to an audio book.
arm group label: Alternative Auditory Stimulation
intervention type: Behavioral
intervention name: No Auditory Stimulation
description: Patients wear headphones for 30 minutes/day over a period of four weeks and hear silence.
arm group label: No Auditory Stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Jens D Rollnik, MD
role: Study Director
affiliation: BDH-Clinic Hessisch Oldendorf
last name: Melanie Boltzmann, PhD
role: Principal Investigator
affiliation: BDH-Clinic Hessisch Oldendorf
last name: Melanie Boltzmann, PhD
phone: 0049 5152 781 256
email: m.boltzmann@bdh-klinik-hessisch.oldendorf
last name: Simone B Schmidt, PhD
phone: 0049 5152 781 215
email: si.schmidt@bdh-klinik-hessisch.oldendorf
facility: 
status: Recruiting
contact: 
country: Germany
citation: Kotchoubey B, Pavlov YG, Kleber B. Music in Research and Rehabilitation of Disorders of Consciousness: Psychological and Neurophysiological Foundations. Front Psychol. 2015 Nov 27;6:1763. doi: 10.3389/fpsyg.2015.01763. eCollection 2015.
PMID: 26640445
citation: Perrin F, Castro M, Tillmann B, Luaute J. Promoting the use of personally relevant stimuli for investigating patients with disorders of consciousness. Front Psychol. 2015 Jul 30;6:1102. doi: 10.3389/fpsyg.2015.01102. eCollection 2015.
PMID: 26284020
citation: Hole J, Hirsch M, Ball E, Meads C. Music as an aid for postoperative recovery in adults: a systematic review and meta-analysis. Lancet. 2015 Oct 24;386(10004):1659-71. doi: 10.1016/S0140-6736(15)60169-6. Epub 2015 Aug 12. Erratum In: Lancet. 2015 Oct 24;386(10004):1630.
PMID: 26277246
citation: Chlan LL, Weinert CR, Heiderscheit A, Tracy MF, Skaar DJ, Guttormson JL, Savik K. Effects of patient-directed music intervention on anxiety and sedative exposure in critically ill patients receiving mechanical ventilatory support: a randomized clinical trial. JAMA. 2013 Jun 12;309(22):2335-44. doi: 10.1001/jama.2013.5670.
PMID: 23689789
citation: Sun J, Chen W. Music therapy for coma patients: preliminary results. Eur Rev Med Pharmacol Sci. 2015 Apr;19(7):1209-18.
PMID: 25912580
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Consciousness Disorders
mesh term: Nervous System Diseases
sharing ipd: Yes
ipd description: All IPD that underlie results in a publication.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Period of availability begins when results are published, at the earliest in Dec 2022
ipd access criteria: IPD can be obtained from the principal investigator upon reasonable request.