<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/NCT04400071</url>
  </required_header>
  <id_info>
    <org_study_id>R01NR019190</org_study_id>
    <secondary_id>R01NR019190</secondary_id>
    <nct_id>NCT04400071</nct_id>
  </id_info>
  <brief_title>Biology and Benefits of Music Play and Stories for Kids/Parents During ALL Treatment</brief_title>
  <official_title>Biologic Mechanisms and Dosing of Active Music Engagement in Children With Acute Lymphoblastic Leukemia and Parents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Children's Mercy Hospital Kansas City</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ann &amp; Robert H Lurie Children's Hospital of Chicago</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Riley Hospital for Children at Indiana University Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Nursing Research (NINR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Indiana University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Music therapy has become a standard palliative care service in many pediatric and adult&#xD;
      hospitals; however, a majority of music therapy research has focused on the use of music to&#xD;
      improve psychosocial dimensions of health, without considering biological dimensions. This&#xD;
      study builds on prior work examining the psychosocial mechanisms of action underlying an&#xD;
      Active Music Engagement (AME) intervention, designed to help manage emotional distress and&#xD;
      improve positive health outcomes in young children with cancer and parents, by examining its&#xD;
      effects on biomarkers of stress and immune function. The purposes of this two group,&#xD;
      randomized controlled trial are to examine biological mechanisms of effect and dose-response&#xD;
      relationships of AME on child/parent stress during the consolidation phase of Acute&#xD;
      Lymphoblastic Leukemia (ALL) treatment. Specific aims are to: Aim 1. Establish whether AME&#xD;
      lowers child and parent cortisol during ALL treatment. Aim 2. Examine cortisol as a mediator&#xD;
      of AME effects on child and parent outcomes during ALL treatment. Aim 3 (exploratory).&#xD;
      Examine the dose-response relationship of AME on child and parent cortisol during ALL&#xD;
      treatment. Findings will provide a more holistic understanding about how active music&#xD;
      interventions work to mitigate cancer-related stress and its potential to improve immune&#xD;
      function, with direct implications for the evidence-based use of music to improve health.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Music therapy has become a standard palliative care service in many pediatric and adult&#xD;
      hospitals. However, a majority of music therapy research has focused on the use of music to&#xD;
      improve psychosocial dimensions of health, without considering biological dimensions. In&#xD;
      addition, few studies have examined dose-response relationships. Cancer treatment is an&#xD;
      inherently stressful experience, and a significant number of young children and parents&#xD;
      (caregivers) experience persistent, interrelated emotional distress and poor quality of life.&#xD;
      Many parents also experience traumatic stress symptoms because of their child's cancer&#xD;
      diagnosis and treatment. The investigators previously tested an Active Music Engagement (AME)&#xD;
      intervention that uses active music play to diminish stressful attributes of cancer treatment&#xD;
      to help manage emotional/traumatic distress experienced by young children (ages 3-8) and&#xD;
      parents and improve quality of life. A recent AME trial is examining psychosocial mechanisms&#xD;
      of action responsible for change in child/parent outcomes. The current study expands on this&#xD;
      work by examining AME's effects on several biomarkers to provide a more holistic&#xD;
      understanding about how active music interventions work to mitigate cancer-related stress and&#xD;
      its potential to improve immune function. The purposes of this two group, randomized&#xD;
      controlled trial are to examine biological mechanisms of effect and dose-response&#xD;
      relationships of AME on child/parent stress during the consolidation phase of Acute&#xD;
      Lymphoblastic Leukemia (ALL) treatment. Specific aims are to: 1) establish whether AME lowers&#xD;
      child and parent cortisol, 2) examine cortisol as a mediator of AME effects on child and&#xD;
      parent outcomes, and 3) examine the dose-response relationship of AME on child and parent&#xD;
      cortisol. Child/parent dyads (n=250) will be stratified (by age, site, ALL risk level) and&#xD;
      randomized in blocks of four to AME or attention control. Each group will receive one&#xD;
      45-minute session during weekly clinic visits for the duration of ALL consolidation (4 weeks&#xD;
      standard risk; 8 weeks high risk). Parents will complete measures at baseline and following&#xD;
      the last study session. Child and parent salivary cortisol samples will be taken pre and&#xD;
      post-session for the first 4 AME or attention control sessions. Child blood samples will be&#xD;
      reserved from routine blood draws prior to sessions 1 and 4 (all participants) and session 8&#xD;
      (high risk participants). Linear mixed models will be used to estimate AME's effect on child&#xD;
      and parent cortisol. Examining child and parent cortisol as mediators of AME effects on child&#xD;
      and parent outcomes will be performed in an ANCOVA setting, fitting the appropriate mediation&#xD;
      models using MPlus and then testing indirect effects using the percentile bootstrap approach&#xD;
      to estimate the indirect effect. Graphical plots and non-linear repeated measures models will&#xD;
      be used to examine the dose-response relationship of AME on child and parent cortisol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 7, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2025</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>Supportive Care</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Study personnel responsible for administering self report measures will be blinded to participant's study condition.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Child and Parent Stress (Salivary Cortisol)</measure>
    <time_frame>Pre/Post-Sessions 1, 2, 3, and 4 (each session is 7 days apart; each session has a 45 min. duration).</time_frame>
    <description>We will measure salivary cortisol (a steroid hormone) as a biological indicator of stress. Cortisol is one of the most frequently used biomarkers for stress and has been used in several cancer studies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Immunomodulatory Cytokines (children only) (blood)</measure>
    <time_frame>Pre-Session Week 1 and Week 4 (all child participants); and Pre-Session Week 8 (only high risk child participants).</time_frame>
    <description>We will measure serum levels of IL-1β, IL-6, TNF-α, IFN-γ, IL-4, IL-10, and IL-13. The activation of the HPA-axis has been reported to shift to promote the secretion of anti-inflammatory cytokines (IL-4, IL-10, IL-13) and decrease pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ) and thus modulate immune function.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Child Health Questionnaire-Mental Health Subscale (CHQ)</measure>
    <time_frame>Baseline; Post-Session Week 4 (standard risk participants); Post-Session Week 8 (high risk participants)</time_frame>
    <description>Measures the frequency of both negative and positive states. Items capture anxiety, depression, and positive affect. We chose the parent-report version due to our targeted child age range of 3-8 years; parent-proxy and child self-report measures are scored differently, so we elected to use parent-proxy for all children. The subscale includes 16 parent-report items on a 5-point Likert-scale, ranging from 1 (none of the time) to 5 (all of the time). Scores range from 16-80 with higher scores indicating better mental health. Across 25 subgroups, the median Cronbach alpha coefficient for the subscale was .76, coefficients ranged from .67 to .86.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in KINDLR Questionnaire for Measuring Health-Related Quality of Life in Children</measure>
    <time_frame>Baseline; Post-Session Week 4 (standard risk participants); Post-Session Week 8 (high risk participants).</time_frame>
    <description>Measures global quality of life. The KINDL is used widely and has been translated into 11 languages. It was selected over other well-known measures for its positive health perspective, especially for younger children. The KINDL consists of 24 parent-report items rated on a 5-point Likert-scale, ranging from 1 (never) to 5 (all the time). There are 6 subscales: Physical well-being, Emotional Well-being, Self-Esteem, Family, Friends, and Everyday Functioning. We will use 20 items in 5 subscales, omitting the Everyday Functioning subscale, because it is focused on school-related functioning and children may not be attending school. Scores range from 20 - 100 with higher scores indicating better quality of life. KINDL parent-report is a valid and reliable measure for children as young as age 3. The KINDL has satisfactory convergent and discriminant validity, and a Cronbach alpha of .89 for the total scale.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Profile of Mood States - Short Form (POMS-SF)</measure>
    <time_frame>Baseline; Post-Session Week 4 (standard risk participants); Post-Session Week 8 (high risk participants).</time_frame>
    <description>Measures mood disturbance. The scale is a self-report, 37-item instrument that yields scores on six subscales (tension-anxiety; depression-dejection; anger-hostility; vigor-activity; fatigue-inertia; confusion-bewilderment) and a total mood disturbance score. Respondents are given 37 adjectives used to describe feelings during the last week and asked to respond to each item using a 5-point Likert scale (0 = not at all; 4 = extremely). Higher scores equal greater mood disturbance. Construct validity is widely supported. The POMS-SF strongly correlates with the original 65-item POMS (r = 0.99) and is one of the most commonly used measures for parent emotional distress in pediatric cancer research.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Impact of Events Scale - Revised (IES-R)</measure>
    <time_frame>Baseline; Post-Session Week 4 (standard risk participants); Post-Session Week 8 (high risk participants).</time_frame>
    <description>A 22-item measure that measures traumatic stress symptoms in response to a traumatic event that is specified in the instructions. In our study, parents will respond to items in reference to their child's cancer treatment as the stressor. The scale includes three subscales: intrusion, avoidance, and hyperarousal. Parents respond to each item using a 5-point Likert scale (0 = not at all; 4 = extremely). Higher scores indicate greater traumatic stress symptoms. The IES-R has been used in studies of childhood cancer patients and their parents. Cronbach's alpha for Intrusion, Avoidance, and Hyperarousal scales were .91, .84, and .90 respectively.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Index of Well-being</measure>
    <time_frame>Baseline; Post-Session Week 4 (standard risk participants); Post-Session Week 8 (high risk participants)</time_frame>
    <description>A 9-item semantic differential scale describing present life using adjective extremes such as discouraging/hopeful. Higher scores mean greater well-being. The scale has well established construct validity and a reported Cronbach alpha of .93 for the total scale.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Acute Lymphoblastic Leukemia, Pediatric</condition>
  <condition>Pediatric Cancer</condition>
  <arm_group>
    <arm_group_label>Active Music Engagement</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>See intervention description.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Audio Storybooks</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>See intervention description.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Active Music Engagement</intervention_name>
    <description>Weekly 45-minute sessions with a board-certified music therapist delivered during weekly clinic visits for the consolidation phase of ALL treatment. Children with standard risk ALL will receive 4 sessions over 4 weeks. Children with high risk ALL will receive 8 sessions over 8 weeks. Sessions are delivered in a private setting during regularly scheduled clinic appointments. During the first visit, parent and child will receive information on how they can use music play activities to help manage distress during treatment. The music therapist will lead parent and child in a variety of music play activities. Parent and child will receive a music kit that includes items such as hand-held rhythm instruments, puppets, and a music CD. During subsequent visits the music therapist will lead parent and child through the music play activities, answer questions, and make suggestions for using these activities in the hospital and at home.</description>
    <arm_group_label>Active Music Engagement</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Audio Storybooks</intervention_name>
    <description>Weekly 45-minute sessions with a trained provider delivered during weekly clinic visits for the consolidation phase of ALL treatment. Children with standard risk ALL will receive 4 sessions over 4 weeks. Children with high risk ALL will receive 8 sessions over 8 weeks. Sessions are delivered in a private setting during regularly scheduled clinic appointments. Each session children/parents will choose and listen to one of three illustrated children's books with audio-recorded narration.</description>
    <arm_group_label>Audio Storybooks</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Child is 3 - 8 years of age at time of enrollment&#xD;
&#xD;
          -  Child has diagnosis of standard or high risk B- or T-cell acute lymphoblastic leukemia&#xD;
             (ALL) or lymphoblastic lymphoma (LyLy)&#xD;
&#xD;
          -  Child is currently receiving induction therapy&#xD;
&#xD;
          -  One parent (&gt;18 years of age) can be present for all sessions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Child has Ph+ ALL,&#xD;
&#xD;
          -  Child has Cushing disease,&#xD;
&#xD;
          -  Child is being treated per AALL0434 Arm B,&#xD;
&#xD;
          -  Child is taking steroid medication for asthma and/or has asthma that is not well&#xD;
             controlled,&#xD;
&#xD;
          -  The parent does not speak English, or&#xD;
&#xD;
          -  The child has a significant cognitive impairment that might hinder participation&#xD;
             (determination made in consultation with attending physician, oncologist, and&#xD;
             parents).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>8 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sheri L Robb, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sheri L Robb, PhD</last_name>
    <phone>317-274-3152</phone>
    <email>shrobb@iu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Claire J Kendrick, MM</last_name>
    <phone>317-278-0853</phone>
    <email>cjkendri@iu.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jenny Shoop, DNP</last_name>
      <email>jshoop@luriechildrens.org</email>
    </contact>
    <investigator>
      <last_name>Jenny Shoop, DNP</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Riley Hospital for Children</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sheri L Robb, PhD</last_name>
      <phone>317-274-3152</phone>
      <email>shrobb@iu.edu</email>
    </contact>
    <contact_backup>
      <last_name>Claire J Kendrick, MM</last_name>
      <phone>317-278-0853</phone>
      <email>cjkendri@iu.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Sheri L Robb, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Susan M Perkins, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Timothy E Stump, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Seethal Jacob, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kristen A Russ, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Steven J Holochwost, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Mercy Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristin Stegenga, PhD</last_name>
      <email>kstegenga@cmh.edu</email>
    </contact>
    <investigator>
      <last_name>Kristin Stegenga, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Robb SL, Clair AA, Watanabe M, Monahan PO, Azzouz F, Stouffer JW, Ebberts A, Darsie E, Whitmer C, Walker J, Nelson K, Hanson-Abromeit D, Lane D, Hannan A. A non-randomized [corrected] controlled trial of the active music engagement (AME) intervention on children with cancer. Psychooncology. 2008 Jul;17(7):699-708. doi: 10.1002/pon.1301. Erratum In: Psychooncology. 2008 Sep;17(9):957.</citation>
    <PMID>18033724</PMID>
  </reference>
  <reference>
    <citation>Robb SL, Haase JE, Perkins SM, Haut PR, Henley AK, Knafl KA, Tong Y. Pilot Randomized Trial of Active Music Engagement Intervention Parent Delivery for Young Children With Cancer. J Pediatr Psychol. 2017 Mar 1;42(2):208-219. doi: 10.1093/jpepsy/jsw050.</citation>
    <PMID>27289068</PMID>
  </reference>
  <reference>
    <citation>Robb SL. The effect of therapeutic music interventions on the behavior of hospitalized children in isolation: developing a contextual support model of music therapy. J Music Ther. 2000 Summer;37(2):118-46. doi: 10.1093/jmt/37.2.118.</citation>
    <PMID>10932125</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>May 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>October 18, 2022</last_update_submitted>
  <last_update_submitted_qc>October 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>Sheri Robb</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04400071
org study id: R01NR019190
secondary id: R01NR019190
nct id: NCT04400071
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Music therapy has become a standard palliative care service in many pediatric and adult
      hospitals; however, a majority of music therapy research has focused on the use of music to
      improve psychosocial dimensions of health, without considering biological dimensions. This
      study builds on prior work examining the psychosocial mechanisms of action underlying an
      Active Music Engagement (AME) intervention, designed to help manage emotional distress and
      improve positive health outcomes in young children with cancer and parents, by examining its
      effects on biomarkers of stress and immune function. The purposes of this two group,
      randomized controlled trial are to examine biological mechanisms of effect and dose-response
      relationships of AME on child/parent stress during the consolidation phase of Acute
      Lymphoblastic Leukemia (ALL) treatment. Specific aims are to: Aim 1. Establish whether AME
      lowers child and parent cortisol during ALL treatment. Aim 2. Examine cortisol as a mediator
      of AME effects on child and parent outcomes during ALL treatment. Aim 3 (exploratory).
      Examine the dose-response relationship of AME on child and parent cortisol during ALL
      treatment. Findings will provide a more holistic understanding about how active music
      interventions work to mitigate cancer-related stress and its potential to improve immune
      function, with direct implications for the evidence-based use of music to improve health.
Music therapy has become a standard palliative care service in many pediatric and adult
      hospitals. However, a majority of music therapy research has focused on the use of music to
      improve psychosocial dimensions of health, without considering biological dimensions. In
      addition, few studies have examined dose-response relationships. Cancer treatment is an
      inherently stressful experience, and a significant number of young children and parents
      (caregivers) experience persistent, interrelated emotional distress and poor quality of life.
      Many parents also experience traumatic stress symptoms because of their child's cancer
      diagnosis and treatment. The investigators previously tested an Active Music Engagement (AME)
      intervention that uses active music play to diminish stressful attributes of cancer treatment
      to help manage emotional/traumatic distress experienced by young children (ages 3-8) and
      parents and improve quality of life. A recent AME trial is examining psychosocial mechanisms
      of action responsible for change in child/parent outcomes. The current study expands on this
      work by examining AME's effects on several biomarkers to provide a more holistic
      understanding about how active music interventions work to mitigate cancer-related stress and
      its potential to improve immune function. The purposes of this two group, randomized
      controlled trial are to examine biological mechanisms of effect and dose-response
      relationships of AME on child/parent stress during the consolidation phase of Acute
      Lymphoblastic Leukemia (ALL) treatment. Specific aims are to: 1) establish whether AME lowers
      child and parent cortisol, 2) examine cortisol as a mediator of AME effects on child and
      parent outcomes, and 3) examine the dose-response relationship of AME on child and parent
      cortisol. Child/parent dyads (n=250) will be stratified (by age, site, ALL risk level) and
      randomized in blocks of four to AME or attention control. Each group will receive one
      45-minute session during weekly clinic visits for the duration of ALL consolidation (4 weeks
      standard risk; 8 weeks high risk). Parents will complete measures at baseline and following
      the last study session. Child and parent salivary cortisol samples will be taken pre and
      post-session for the first 4 AME or attention control sessions. Child blood samples will be
      reserved from routine blood draws prior to sessions 1 and 4 (all participants) and session 8
      (high risk participants). Linear mixed models will be used to estimate AME's effect on child
      and parent cortisol. Examining child and parent cortisol as mediators of AME effects on child
      and parent outcomes will be performed in an ANCOVA setting, fitting the appropriate mediation
      models using MPlus and then testing indirect effects using the percentile bootstrap approach
      to estimate the indirect effect. Graphical plots and non-linear repeated measures models will
      be used to examine the dose-response relationship of AME on child and parent cortisol.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Single (Outcomes Assessor)
masking description: Study personnel responsible for administering self report measures will be blinded to participant's study condition.
measure: Change in Child and Parent Stress (Salivary Cortisol)
time frame: Pre/Post-Sessions 1, 2, 3, and 4 (each session is 7 days apart; each session has a 45 min. duration).
description: We will measure salivary cortisol (a steroid hormone) as a biological indicator of stress. Cortisol is one of the most frequently used biomarkers for stress and has been used in several cancer studies.
measure: Change in Immunomodulatory Cytokines (children only) (blood)
time frame: Pre-Session Week 1 and Week 4 (all child participants); and Pre-Session Week 8 (only high risk child participants).
description: We will measure serum levels of IL-1β, IL-6, TNF-α, IFN-γ, IL-4, IL-10, and IL-13. The activation of the HPA-axis has been reported to shift to promote the secretion of anti-inflammatory cytokines (IL-4, IL-10, IL-13) and decrease pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ) and thus modulate immune function.
measure: Change in Child Health Questionnaire-Mental Health Subscale (CHQ)
time frame: Baseline; Post-Session Week 4 (standard risk participants); Post-Session Week 8 (high risk participants)
description: Measures the frequency of both negative and positive states. Items capture anxiety, depression, and positive affect. We chose the parent-report version due to our targeted child age range of 3-8 years; parent-proxy and child self-report measures are scored differently, so we elected to use parent-proxy for all children. The subscale includes 16 parent-report items on a 5-point Likert-scale, ranging from 1 (none of the time) to 5 (all of the time). Scores range from 16-80 with higher scores indicating better mental health. Across 25 subgroups, the median Cronbach alpha coefficient for the subscale was .76, coefficients ranged from .67 to .86.
measure: Change in KINDLR Questionnaire for Measuring Health-Related Quality of Life in Children
time frame: Baseline; Post-Session Week 4 (standard risk participants); Post-Session Week 8 (high risk participants).
description: Measures global quality of life. The KINDL is used widely and has been translated into 11 languages. It was selected over other well-known measures for its positive health perspective, especially for younger children. The KINDL consists of 24 parent-report items rated on a 5-point Likert-scale, ranging from 1 (never) to 5 (all the time). There are 6 subscales: Physical well-being, Emotional Well-being, Self-Esteem, Family, Friends, and Everyday Functioning. We will use 20 items in 5 subscales, omitting the Everyday Functioning subscale, because it is focused on school-related functioning and children may not be attending school. Scores range from 20 - 100 with higher scores indicating better quality of life. KINDL parent-report is a valid and reliable measure for children as young as age 3. The KINDL has satisfactory convergent and discriminant validity, and a Cronbach alpha of .89 for the total scale.
measure: Change in Profile of Mood States - Short Form (POMS-SF)
time frame: Baseline; Post-Session Week 4 (standard risk participants); Post-Session Week 8 (high risk participants).
description: Measures mood disturbance. The scale is a self-report, 37-item instrument that yields scores on six subscales (tension-anxiety; depression-dejection; anger-hostility; vigor-activity; fatigue-inertia; confusion-bewilderment) and a total mood disturbance score. Respondents are given 37 adjectives used to describe feelings during the last week and asked to respond to each item using a 5-point Likert scale (0 = not at all; 4 = extremely). Higher scores equal greater mood disturbance. Construct validity is widely supported. The POMS-SF strongly correlates with the original 65-item POMS (r = 0.99) and is one of the most commonly used measures for parent emotional distress in pediatric cancer research.
measure: Change in Impact of Events Scale - Revised (IES-R)
time frame: Baseline; Post-Session Week 4 (standard risk participants); Post-Session Week 8 (high risk participants).
description: A 22-item measure that measures traumatic stress symptoms in response to a traumatic event that is specified in the instructions. In our study, parents will respond to items in reference to their child's cancer treatment as the stressor. The scale includes three subscales: intrusion, avoidance, and hyperarousal. Parents respond to each item using a 5-point Likert scale (0 = not at all; 4 = extremely). Higher scores indicate greater traumatic stress symptoms. The IES-R has been used in studies of childhood cancer patients and their parents. Cronbach's alpha for Intrusion, Avoidance, and Hyperarousal scales were .91, .84, and .90 respectively.
measure: Change in Index of Well-being
time frame: Baseline; Post-Session Week 4 (standard risk participants); Post-Session Week 8 (high risk participants)
description: A 9-item semantic differential scale describing present life using adjective extremes such as discouraging/hopeful. Higher scores mean greater well-being. The scale has well established construct validity and a reported Cronbach alpha of .93 for the total scale.
arm group label: Active Music Engagement
arm group type: Experimental
description: See intervention description.
arm group label: Audio Storybooks
arm group type: Active Comparator
description: See intervention description.
intervention type: Behavioral
intervention name: Active Music Engagement
description: Weekly 45-minute sessions with a board-certified music therapist delivered during weekly clinic visits for the consolidation phase of ALL treatment. Children with standard risk ALL will receive 4 sessions over 4 weeks. Children with high risk ALL will receive 8 sessions over 8 weeks. Sessions are delivered in a private setting during regularly scheduled clinic appointments. During the first visit, parent and child will receive information on how they can use music play activities to help manage distress during treatment. The music therapist will lead parent and child in a variety of music play activities. Parent and child will receive a music kit that includes items such as hand-held rhythm instruments, puppets, and a music CD. During subsequent visits the music therapist will lead parent and child through the music play activities, answer questions, and make suggestions for using these activities in the hospital and at home.
arm group label: Active Music Engagement
intervention type: Behavioral
intervention name: Audio Storybooks
description: Weekly 45-minute sessions with a trained provider delivered during weekly clinic visits for the consolidation phase of ALL treatment. Children with standard risk ALL will receive 4 sessions over 4 weeks. Children with high risk ALL will receive 8 sessions over 8 weeks. Sessions are delivered in a private setting during regularly scheduled clinic appointments. Each session children/parents will choose and listen to one of three illustrated children's books with audio-recorded narration.
arm group label: Audio Storybooks
criteria: 
gender: All
minimum age: 3 Years
maximum age: 8 Years
healthy volunteers: No
last name: Sheri L Robb, PhD
role: Principal Investigator
affiliation: Indiana University
last name: Sheri L Robb, PhD
phone: 317-274-3152
email: shrobb@iu.edu
last name: Claire J Kendrick, MM
phone: 317-278-0853
email: cjkendri@iu.edu
facility: 
status: Recruiting
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status: Recruiting
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country: United States
citation: Robb SL, Clair AA, Watanabe M, Monahan PO, Azzouz F, Stouffer JW, Ebberts A, Darsie E, Whitmer C, Walker J, Nelson K, Hanson-Abromeit D, Lane D, Hannan A. A non-randomized [corrected] controlled trial of the active music engagement (AME) intervention on children with cancer. Psychooncology. 2008 Jul;17(7):699-708. doi: 10.1002/pon.1301. Erratum In: Psychooncology. 2008 Sep;17(9):957.
PMID: 18033724
citation: Robb SL, Haase JE, Perkins SM, Haut PR, Henley AK, Knafl KA, Tong Y. Pilot Randomized Trial of Active Music Engagement Intervention Parent Delivery for Young Children With Cancer. J Pediatr Psychol. 2017 Mar 1;42(2):208-219. doi: 10.1093/jpepsy/jsw050.
PMID: 27289068
citation: Robb SL. The effect of therapeutic music interventions on the behavior of hospitalized children in isolation: developing a contextual support model of music therapy. J Music Ther. 2000 Summer;37(2):118-46. doi: 10.1093/jmt/37.2.118.
PMID: 10932125
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: Sheri Robb
investigator title: Professor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
sharing ipd: No