Assessing Molecular Mechanisms and Effects of Music Therapy in Youth With Sickle Cell Disease Using Single-cell RNA-sequencing

The goal of this clinical trial is to evaluate whether a 4-week music therapy (MT) intervention can reduce chronic pain and improve psychosocial outcomes in youth with sickle cell disease (SCD).

The main questions it aims to answer are:

• Does MT reduce pain intensity, frequency of pain episodes, and improve health-related quality of life (HRQoL)?
• Does MT alter immune cell composition and gene expression in inflammatory pathways, as measured by single-cell RNA sequencing (scRNA-seq)?

Researchers will compare participants randomized to music therapy versus a control condition to see if MT produces superior improvements in pain and psychosocial outcomes, and distinct molecular changes.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Other: Music Therapy; Other: Standard of Care

Detailed Description

Sickle cell disease (SCD) is an inherited blood disorder that affects approximately 100,000 individuals in the United States, with higher prevalence among people of African and Latin-American descent. Children and adolescents with SCD often experience recurrent vaso-occlusive episodes (VOE) and chronic pain, which contribute to emotional distress, impaired academic performance, reduced daily functioning, and increased hospital utilization. Chronic pain also imposes a substantial financial burden and is associated with anxiety, depression, and diminished quality of life. Current pharmacologic treatments, such as hydroxyurea and blood transfusions, can reduce pain crises but are limited by side effects that interfere with school attendance and social participation, underscoring the need for safe, nonpharmacologic alternatives. Integrative approaches, such as cognitive behavioral therapy (CBT) and music therapy (MT), have been recognized as effective non-pharmacological pain management strategies, with evidence showing improvements in pain, mood, fatigue, and overall quality of life. However, the molecular mechanisms underlying these benefits remain poorly understood, particularly in SCD.

This study will evaluate the effects of a 4-week MT intervention in youth with SCD, focusing on both psychosocial outcomes and molecular mechanisms. The intervention will be delivered using Music Care©, a virtual platform that employs a structured "U" algorithm, beginning with stimulating music, transitioning into relaxation, and concluding with a gentle reintroduction of rhythm and energy. The primary aim is to determine whether MT reduces pain intensity, frequency of pain episodes, stress, anxiety, depression, and improves health-related quality of life (HRQoL). The secondary aim is to investigate changes in immune cell composition and gene expression using single-cell RNA sequencing (scRNA-seq), which will enable detailed profiling of immune cells, including T cells, B cells, monocytes, neutrophils, and granulocytes, as well as their transcriptional states and regulatory networks. Samples will be collected at baseline and endpoint to identify pathways altered by MT and to correlate molecular findings with clinical outcomes.

By integrating psychosocial assessments with single-cell transcriptomic profiling, this study seeks to provide novel insights into how MT modulates immune and inflammatory pathways in pediatric SCD. Understanding these mechanisms may reveal new therapeutic targets, improve patient stratification, and support broader adoption of MT as an evidence-based, nonpharmacologic intervention for chronic pain management in children and adolescents living with SCD.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Manoj Bhasin, PhD; Phone Number: 404-712-9849; Email: manoj.bhasin@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30324
      • Recruiting
      • Children's Healthcare of Atlanta
      • Contact: Soumitri Sil, PhD; Phone Number: 404-727-2712; Email: soumitri.sil@emory.edu
      • Sub-Investigator: Soumitri Sil, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with SCD
• English fluency (for survey completion)
• Have access to a personal electronic device (e.g., phone, tablet) with access to the internet

• Meet the criteria for chronic pain defined by the International Association for the Study of Pain (IASP). IASP defines chronic pain as pain that is both:

  1. Persistent or recurrent for ≥ 3 months
  2. is associated with significant emotional distress or functional disability.30

Exclusion Criteria:

• Major hearing deficiency or medical condition in which listening to music may be contraindicated (e.g., reflex epilepsy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Music Therapy group; The MT group will engage in 20-minute daily virtual music therapy sessions for 4 weeks, using the freely available Music Care© app (manufactured by MUSIC CARE) to independently participate in electronic music therapy following the U sequence. This app is voluntarily downloaded onto a participant's personal device, and participants will be instructed to complete daily MT sessions under optimal conditions (i.e., lying down, eyes closed, low lighting).	Other: Music Therapy; The MT group will engage in 20-minute daily virtual music therapy sessions for 4 weeks, using the freely available Music Care© app (manufactured by MUSIC CARE) to independently participate in electronic music therapy following the U sequence. This app is voluntarily downloaded onto a participants personal device and participants will be instructed to complete daily MT sessions under optimal conditions (i.e., lying down, eyes closed, low lighting).; Other Names: MT
Sham Comparator: Control group; The control group will be asked to engage with educational material for 20 minutes daily. There will be no restrictions for research subjects in regards to listening to music under other conditions (e.g., phone, radio, concert, etc)	Other: Standard of Care; Routinely available educational material on sickle cell disease management and a healthy lifestyle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain characteristics	The Brief Pain Inventory (BPI) is a validated self-report questionnaire that measures both the severity of pain and the degree to which pain interferes with daily activities. Pain intensity is rated on a 0-10 numeric scale (0 = no pain, 10 = worst pain imaginable). Pain interference items are also scored 0-10 (0 = does not interfere, 10 = completely interferes). Greater scores indicate more severe pain and greater interference with daily activities.	Baseline, Week 5
Change in Health-related quality of life (HRQoL)	Parents will complete the Pediatric Quality of Life Inventory (PedsQL) at baseline and Week 5. This parent-proxy measure assesses physical, emotional, social, and school functioning. Changes in HRQoL scores will be analyzed to determine whether music therapy improves overall well-being compared to control. Scoring: Items are scored on a 0-100 scale, with higher scores reflecting better quality of life (less impairment). Lower scores indicate poorer functioning across physical, emotional, social, and school domains.	Baseline, Week 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depressive Symptoms	Youth participants will complete the Patient Health Questionnaire (PHQ-8) at baseline and Week 5. This validated tool measures the frequency and severity of depressive symptoms. Each item scored 0-3 (0 = not at all, 3 = nearly every day). Total score range: 0-24. Higher scores indicate greater severity of depressive symptoms.	Baseline, Week 5
Change in General Anxiety Disorder scale scores	The General Anxiety Disorder scale (GAD-2) will be administered at baseline and Week 5. This brief self-report tool screens for generalized anxiety symptoms. Each item scored 0-3, total score range: 0-6. Higher scores indicate greater anxiety symptoms.	Baseline, Week 5
Change in Psychological Stress	The PROMIS Pediatric Short Form - Psychological Stress will be collected at baseline and Week 5 to assess perceived psychological stress. Items scored on a 5-point Likert scale. Raw scores are converted to T-scores (mean = 50, SD = 10). Higher T-scores indicate greater psychological stress.	Baseline, Week 5
Change in Physical stress	The PROMIS Pediatric Short Form - Physical Stress will be collected at baseline and Week 5 to measure somatic stress symptoms. Items scored on a 5-point Likert scale. Raw scores are converted to T-scores (mean = 50, SD = 10). Higher T-scores indicate greater psychological stress.	Baseline, Week 5
Hospital utilization	The number of hospitalizations or pain-related treatments during the 4-week study will be tracked through medical chart review and participant report.	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene expression changes in immune cells	gene expression changes in immune cells (T cells, B cells, monocytes, neutrophils, granulocytes). Assessed via single-cell RNA sequencing (scRNA-seq)	Baseline, Week 5

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Manoj Bhasin, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 27, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Sickle cell disease; Music therapy; Pain control
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, Inborn; Neurobehavioral Manifestations; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Perceptual Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Agnosia; Health Services Administration; Health Care Quality, Access, and Evaluation; Therapeutics; Quality of Health Care; Complementary Therapies; Quality Indicators, Health Care; Patient Care; Psychotherapy; Behavioral Disciplines and Activities; Rehabilitation; Aftercare; Continuity of Patient Care; Sensory Art Therapies; Standard of Care; Music Therapy
• Other Study ID Numbers: 2025P012013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the publication will be shared after de-identification
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following publication
• IPD Sharing Access Criteria: Investigators whose proposed use of the data is provided in a formal written request, has been approved by the IRB, and receives explicit PI approval. Proposals may be submitted up to 36 months following publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No