Protocol and biomarker strategy for a multi-site randomized controlled trial examining biological mechanisms and dosing of active music engagement in children with acute lymphoblastic leukemia and lymphoma and parents

Abstract

Background Music therapy is a standard palliative care service in many pediatric and adult hospitals; however, most 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 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 (caregivers), by examining its effects on biomarkers of stress and immune function. Methods This two-group randomized controlled trial (R01NR019190) is designed to examine biological mechanisms of effect and dose-response relationships of AME on child/parent stress during the consolidation phase of Acute B- or T-cell Lymphoblastic Leukemia (ALL) and T-cell Lymphoblastic Lymphoma (TLyLy) treatment. Child/parent dyads (n = 228) are stratified (by age, site, risk level) and randomized in blocks of four to the AME or attention control condition. Each group receives one session (30-minutes AME; 20-minutes control) during weekly clinic visits (4 weeks standard risk B-cell ALL; 8 weeks high risk B-cell ALL/T-cell ALL/TLyLy). Parents complete questionnaires at baseline and post-intervention. Child/parent salivary cortisol samples are taken pre- and post-session (sessions 1–4). Child blood samples are reserved from routine draws before sessions 1 and 4 (all participants) and session 8 (high risk participants). We will use linear mixed models to estimate AME’s effect on child/parent cortisol. Examining child/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. Graphical plots and non-linear repeated measures models will be used to examine dose-response relationship of AME on child/parent cortisol. Discussion During pediatric cancer treatment there are special challenges that must be considered when measuring cortisol and immune function. In this manuscript we discuss how we addressed three specific challenges through our trial design. Findings from this trial will increase mechanistic understanding of the effects of active music interventions on multiple biomarkers and understanding of dose-response effects, with direct implications for clinical practice. Trial Registration ClinicalTrials.gov: NCT04400071.

Shifting perspectives and transformative change: Parent perspectives of an active music engagement intervention for themselves and their child with cancer

“…Additional research is needed to explore the benefits of AME over an early and longer course of treatment, and to ensure the intervention is culturally relevant and meaningful for all families. In our current trial, children are receiving the same chemotherapy regimen within a couple of months of diagnosis to increase the homogeneity of the timepoint and provide support earlier in the treatment trajectory 49 . Focus groups will explore perspectives of parents from underrepresented racial and ethnic backgrounds to ensure AME content and experiences are meaningful and relevant.…”

“…In our current trial, children are receiving the same chemotherapy regimen within a couple of months of diagnosis to increase the homogeneity of the timepoint and provide support earlier in the treatment trajectory. 49 Focus groups will explore perspectives of parents from underrepresented racial and ethnic back-…”

Interaction-focused music therapy with cancer-affected children and their significant others: a randomized controlled feasibility study with subsequent intervention (INMUT)

“… Quantitative studies : In their RCT, Robb et al report improvement in health outcomes of courageous coping, social integration, and family environment during high-risk cancer treatment using therapeutic music video interventions [ 10 ]. Another RCT and a single case design pilot study from Robb et al point out the positive effects of active music interventions on multiple biomarkers to improve understanding of dose–response effects [ 20 , 21 ], as well as treatment fidelity in music-based play interventions for young children with cancer and their parents [ 22 ]. In addition, a pilot RCT by Robb et al investigated the feasibility and acceptability of parent-delivered active music engagement.…”

“…In the studies we evaluated and selected for this purpose, evidence was found that music-based interventions have positive effects on psychological well-being [ 17 , 24 ], competence, resilience, and interactive affect regulation [ 14 ]. Positive effects have been found in relation to cognitive and physiological aspects [ 12 ], as indicated by biomarkers in form of cortisol and immune function measurements [ 20 , 21 ] and measurement of heart rates, respiratory rates, and blood pressure [ 29 ]. Music therapy has also been claimed to support family functioning and social integration [ 10 , 16 , 18 , 19 , 30 ].…”