Mechanisms Within the Autonomic Nervous SysTEm undeRlying MusIc Therapy's aNalgesic Effects in Sickle Cell Disease (MASTERMIND)

Sickle cell disease causes very painful episodes that can happen without warning. Pain is one of the biggest problems for people with SCD. Medicines like opioids can help, but they have serious side effects. Doctors are looking for other ways to treat pain.

Investigators have already found that music therapy - breathing exercises guided by a trained music therapist - can lower pain in adults with SCD. But investigators don't know exactly how it works yet inside the body.

This study will look at two possible reasons why music therapy helps:

• It may calm the body's "fight-or-flight" (sympathetic) nervous system, which can make pain worse when it is too active.
• It may boost the "calming" (parasympathetic) nervous system, which may ease pain and reduce inflammation.
• It may lower swelling and inflammation in the body, which also drives pain.

Study Overview

• Status: Not yet recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Behavioral: Music Therapy

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kaitlyn Super; Phone Number: 216-844-1800; Email: kaitlyn.super@uhhospitals.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals
      • Contact: Kaitlyn Super; Phone Number: 216-844-1800; Email: kaitlyn.super@uhhospitals.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1) are age ≥18 years
• (2) have a diagnosis of SCD documented in the electronic health record (EHR)--- (3) meet Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy (AAPT) criteria for chronic SCD pain
• (4) are able to speak and understand English
• (5) have an email address and access to a mobile device with a functioning data plan (to get pain diaries)
• (6) report that pain interfered with daily activities at least 1-2 days in past week will be eligible for the study. -

Exclusion Criteria:

• (1) have < 3 vaso-occlusive crises (VOCs) per year and no VOCs in the past 3 months
• (2) have significant visual, hearing, psychiatric or cognitive impairment
• (3) are currently engaged in mind-body therapies under the supervision of a healthcare professional specifically for pain management
• (4) have a planned major medical event in next 8 weeks (e.g., childbirth, orthopedic surgery, gene therapy, stem cell transplant) that does not include routine disease modifying therapies (e.g., blood transfusions)
• (5) are unable or unwilling to refrain from stopping all medications that interfere with the autonomic nervous system for 5 half-lives prior to autonomic testing and from changing their medication regimen during the 2 weeks that separate autonomic testings and blood draws
• (6) develop active VOC requiring hospitalization at enrollment
• (7) have conditions that would significantly affect autonomic testing interpretation, such as severe arrhythmias or pregnancy, will be excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Music Therapy; The MT-BC will engage the participant in a 20-minute deep breathing exercise with live music beating at a defined tempo. Participants will repeat this session on their own.	Behavioral: Music Therapy; Participants will undergo a 20-minute music therapy session with a board certified music therapist, then will repeat this on their own once daily for 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in electrodermal activity (EDA) as measured by change in electrical potential at the surface of the skin	Lower EDA reflects less sympathetic tone	Baseline and after 2 weeks
Change in Quantitative Sudomotor Axon Reflex Test (QSART) as measured by sweat output values	Lower QSART values reflect less sympathetic activity	Baseline and after 2 weeks
Changes in Pupillometry parameters as measured by constriction velocity	Faster constriction velocity indicates a higher pupillary vagal tone.	Baseline and after 2 weeks
Changes in Pupillometry parameters as measured by percent reflex amplitude	Larger percentage of reflex amplitude indicates higher pupillary vagal tone.	Baseline and after 2 weeks
Changes in Pupillometry parameters as measured by dilation velocity.	Slower dilation velocity indicates lower pupillary sympathetic tone.	Baseline and after 2 weeks.
Change in Heart Rate Response to deep breathing	Increased heart rate response to deep breathing denotes increased cardiovagal tone.	Baseline and after 2 weeks
Measurement of average supine resting Blood Pressure (BP)	Lower average resting BP denote lower cardiac sympathetic tone	Baseline and after 2 weeks
Measurement of average supine resting Heart Rate (HR)	Lower average resting HR denote lower cardiac sympathetic tone	Baseline and after 2 weeks
Change in supine resting respiratory rate	A lower resting respiratory rate reflects a shift of autonomic balance toward parasympathetic (vagal) dominance with reduced central sympathetic outflow.	Baseline and after 2 weeks
Change in the maximum heart rate during the Valsalva maneuver	An increased Valsalva Ratio (maximum heart rate to the minimum heart rate) reflects an increase in cardiac parasympathetic tone.	Baseline and after 2 weeks
Change in the minimum heart rate shortly after the Valsalva maneuver	An increased Valsalva Ratio (maximum heart rate to the minimum heart rate) reflects an increase in cardiac parasympathetic tone.	Baseline and after 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in C Reactive Protein as measured by bloodwork	Lower levels of CRP indicate lower levels of inflammation	Baseline and after 2 weeks
Change in Cytokine levels as measured by bloodwork	Lower levels of cytokines indicate lower levels of inflammation	Baseline and after 2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity changes as measured by the Visual Analog Scale (VAS)	The VAS is a straight 100 mm line-usually horizontal-with descriptive word anchors at each end representing opposite extremes of a subjective experience, such as 0 being "no pain" and 10 being "worst possible pain".	Baseline and after 2 weeks of daily music therapy
Pain intensity changes as measured by the Brief Pain Inventory (BPI)	Brief Pain Inventory (BPI) is a self-administered questionnaire used to evaluate pain severity and how pain interferes with daily life on scales from 0 to 10, with 0 being no pain, and 10 being severe pain.	Baseline and after 2 weeks of daily music therapy
Pain diaries	Daily pain intensity and analgesic use	Daily for 2 weeks
Music therapy adherence	Daily log of adherence to the home-based music therapy protocol	Daily for 2 weeks

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Investigators: Principal Investigator: Kamal R Chémali, MD, University Hospitals

Study record dates

Study Major Dates

• Study Start (Estimated): January 2, 2027
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: October 14, 2026
• First Submitted That Met QC Criteria: November 4, 2026
• First Posted (Actual): November 10, 2026

Study Record Updates

• Last Update Posted (Actual): November 10, 2026
• Last Update Submitted That Met QC Criteria: November 4, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; Pain; Autonomic; Music Therapy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Pathologic Processes; Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Pain; Inflammation; Anemia, Sickle Cell; Therapeutics; Complementary Therapies; Patient Care; Psychotherapy; Behavioral Disciplines and Activities; Rehabilitation; Aftercare; Continuity of Patient Care; Sensory Art Therapies; Music Therapy
• Other Study ID Numbers: STUDY20260271

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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