The Mechanism Underlying the Analgesic Effect of the Music of IBS Pain

Not Applicable

Not yet recruiting

• Conditions: Abdominal Pain/ Discomfort; Irritable Bowel Syndrome

• Registration Number: NCT06706778
• Lead Sponsor: Yale University

Brief Summary

The proposed pilot study aims to assess the underlying mechanisms of the MBI on IBS pain and the feasibility of using novel technology in the outcome measurements. The specific aims of this pilot mechanistic clinical trial are to:

1. . identify the mechanisms underlying the impact of MBI on IBS-related pain, stress responses, quantitative pain sensitivity, and gut microbiome profiles.

2. . evaluate the technological feasibility of using a wearable abdominal sensor belt and smartwatch system in measuring MBI impacts on pain in home settings.

Researchers will conduct a one-arm pre- and post-music intervention among patients with Irritable Bowel Syndrome, collect the IBS pain mechanistic biobehavioral markers, and analyze the underlying pathways of the music analgesic effect.

Participants will be asked to:

1. . engage in a 4-week intervention of 20 minutes, both during the day and at night, for at least five days per week.

2. . have two one-hour lab visits

Detailed Description

Purpose The proposed pilot study aims to assess the underlying mechanisms of the MBI on IBS pain and the feasibility of using novel technology in the outcome measurements. Irritable bowel syndrome (IBS) is the most common disorder of brain-gut interactions, characterized primarily by recurrent chronic abdominal pain, which severely impacts the quality of life and productivity of affected individuals, particularly women and young adults. Music-based interventions (MBIs) have shown promise in reducing pain cognitive processing and stress, potentially influencing pain perception in the brain and physiological arousal in the autonomic nervous system (ANS). Therefore, MBIs hold promising therapeutic potential for IBS pain management by targeting the overlapping mechanical pathways in the brain-gut axis (BGA).

Objectives The objective 1 is to identify the mechanisms underlying the impact of MBI on IBS-related pain, stress responses, quantitative pain sensitivity, and gut microbiome profiles.

The objective 2 is to evaluate the technological feasibility of using a wearable abdominal sensor belt and smartwatch system in measuring MBI impacts on pain in home settings.

Study Population In this pilot study, 30 participants with diagnosis of IBS will be recruited. The study focuses on this population because recurrent abdominal pain, discomfort, and altered bowel habits are the core clinical symptoms of patients with IBS. The prevalence of IBS is around 20% in the United States, with annual direct costs of care and indirect lost study/work productivity estimated at more than $21 billion in the United States.

Number of Participants Investigators plan to recruit 30 participants diagnosed with IBS for this pilot study. The sample size is based on investigators' prior experience and the recommended sample size for a pilot study to provide precise estimates.

Study Design This pilot mechanistic study is a one-arm pre- and post- intervention design. The pathways underlying neural and physiologic response to music and brain-gut interaction among IBS patients provide a cue to understand the complex interplay of outcome variables. Participants will be engaged in MBI for 20 minutes during the day and at night, at least five days a week, with the abdominal belt and smartwatch data acquisition during a four-week home-based intervention period. Throughout the study period, investigators will collect IBS pain mechanistic biobehavioral makers, including all real-time visceral pain indicators collected via the abdominal belt, real-time visual analog scale (VAS) pain report by smartwatch, and self-reported pain and stress status. Additionally, investigators will collect stool samples to investigate gut microbiome profiles and assess pain sensitivity through quantitative sensory testing (QST) equipment at two lab visits. Functional regression models and pathway analysis will determine the association between these factors.

Study Duration The pilot study will last for one year. Participants will attend two lab visits, each lasting approximately one hour. After the first lab visit, participants will be asked to engage in a music-based intervention using an abdominal belt and a smartwatch for 20 minutes, both during the day and at night, for at least five days per week. Weekly 15-minute meetings of the research assistants with each participant will be scheduled to follow up on issues encountered.

Outcome Variables Investigators will collect mechanistic biobehavioral markers of IBS pain, including real-time visceral pain indicators (electrodermal activity (EDA), electrocardiogram (ECG), and electromyogram (EMG)) via the abdominal belt, real-time visual analog scale (VAS) pain reports via the smartwatch, self-reported pain, stool samples, and quantitative pain sensitivity testing data. Additionally, investigators will assess participants' adherence to study protocols, completeness of data collection, and post-intervention satisfaction.

Locations/Facilities Participants' lab visits will take place at the Yale School of Nursing (YSN) Center for Biobehavioral Health Research and the Biobehavioral Research Laboratory (BBL). Research assistants will schedule weekly online meetings via Zoom with participants to gather feedback and address any issues encountered. Recruitment will be conducted through advertisements at collaborating gastrointestinal (GI) specialist offices and clinics affiliated with Yale New Haven Hospital. An advertising poster will be attached to bulletin boards on Yale west and main campus in order to draw attention from prospective participants.

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-11-20
• Study First Submitted QC: 2024-11-25
• Last Update Submitted: 2024-11-25
• Study First Posted: 2024-11-27
• Last Update Posted: 2024-11-27
• Study Start: 2025-06-01
• Primary Completion: 2026-06-01
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• aged between 18 and 50 years old,
• can speak and read English,
• having a confirmed diagnosis of IBS from a healthcare provider,
• having experienced moderate pain (≥3 out of 10 on a numeric rating scale) at least four days a week for the past three months,
• be willing to participate in a 4-week intervention and attend two lab visits, and
• having daily access to an internet-enabled device for MBI.

Exclusion Criteria

• having a severe psychiatric disorder requiring inpatient treatment in the past six months,
• regularly using opioids or illicit substances, or have used probiotics or antibiotics within two weeks prior to enrollment,
• having celiac disease, inflammatory bowel disease, or a history of major gastrointestinal surgery,
• concurrently participate in another IBS-related intervention study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
IBS visceral pain index	From intervention enrollment to the end of treatment at 4 weeks	The sensitive objective integrated multimodal electrophysiological (OIME) index will be used as a biomarker for visceral pain evaluation, which will anticipate achieving robust and objective prediction of the pain level. Via machine learning and deep learning analysis, we will quantify the pain level based on key indices from time- and frequency-domain analysis of the objective EDA, ECG, and EMG recordings collected from the abdominal belt.
Real-time self-reported pain	From intervention enrollment to the end of treatment at 4 weeks	The visual analog scale ranging from 0 (no pain) to 100 (highest level of pain) will be used to reflect the real-time episodes of visceral pain.
Brief Pain Inventory	through study completion, an average of 1 year	The 9-item Brief Pain Inventory (BPI) scale sensitively assesses the severity of pain, the most painful area, the impact of pain on daily functions, medications, and the change in pain relief in the past 24 hours and the past week on a 0-10 (0= no pain or interference, 10= the worst possible pain or complete interference); A higher mean score indicates greater severity or interference. Cronbach alpha ranges from 0.77-0.91.
Pain sensitivity	through study completion, an average of 1 year	We will assess participants' peripheral and central pain sensitivity using the comprehensive QST equipment established by the German Research Network on Neuropathic Pain as a protocol to examine thermal and mechanical sensory function44. The QST assessment includes (1) cutaneous mechanical pain sensitivity, which measures tolerance, threshold, temporal summation, and after-sensations; (2) heat and cold pain sensitivity, assessing threshold, tolerance, and ratings of supra-threshold stimuli; and (3) pressure pain thresholds. Quantifying sensory alterations in the IBS patient population offers insight into pain modulatory systems, both pain facilitation (hyperalgesia) and pain inhibition (hypoalgesia)
IBS-quality of life (IBS-QOL)	through study completion, an average of 1 year	The IBS-QOL is a 34-item self-report questionnaire with a five-point Likert scale. It is specifically designed to measure the QOL in individuals with IBS. Total scores are calculated by adding up all the item responses, with higher scores indicating a better QOL. Psychometric evaluations have shown that the IBS-QOL is reliable, with a Cronbach's alpha of 0.96. It also demonstrates strong construct validity and is highly sensitive to detecting changes undergoing interventions.
16S rRNA Gene-based Analysis of Gut Microbiota	through study completion, an average of 1 year	Our team has established the protocols for stool sample collection and processing and tested them in preliminary studies. Stool samples will be collected by a researcher-provided OMNIgene●GUT microbiome collection kit (DNA Genotek, Inc.); this easy self-collection system allows for stabilizing samples at room temperature for 14 days. RAs will provide adequate information and training to the participants about stool collection using the kits at in-person lab visits. Participants can return the samples to the repository by mail using a researcher-provided envelope. Samples will be immediately frozen upon collection at -80° C in the YSN BBL. Samples will be assigned a unique ID number, systematically entered into the specimen repository and database, and profiled by 16S rRNA Illumina sequencing. Paired-end 16S rRNA gene sequencing and analysis will be performed at the University of Connecticut Microbial Analysis, Resources, and Services (MARS) facility on an Illumina MiSeq system.

Secondary Outcome Measures

Name	Time	Method
Perceived Stress Scale-10 (PSS-10)	through study completion, an average of 1 year	PSS-10 will be used to self-report the level of perceived stress in various life situations. It includes ten items rated on a 5-point scale, from "never" to "very often." The total score can range from 0 to 40, with a higher score indicating a higher stress level. The PSS has demonstrated high internal consistency and test-retest reliability.
Feasibility of using new technology in outcome measurements	From enrollment to the end of treatment at 4 weeks	The feasibility of utilizing wearable devices for pain and stress measurement will be evaluated based on participant adherence to study protocols, data collection completeness, and participants' satisfaction. These data will provide insight into the practicality of integrating bio-signal monitoring technology in objective outcome measurements.
Intervention Adherence	through study completion, an average of 1 year	Adherence will be tracked through the number of participants following the protocol over time, including daily usage patterns. Participants will log the frequency, timing, and duration of device usage in a structured online diary using the REDCap system.
Data recording completeness	through study completion, an average of 1 year	Data recording completeness will be assessed by analyzing device synchronization and the proportion of missing data. Retention rates will be calculated based on participant continuity throughout the study duration.
Participant satisfaction	From intervention enrollment to the end of treatment at 4 weeks	Post-intervention surveys will be administered to assess participant satisfaction, complemented by weekly feedback meetings to capture ongoing impressions and address any barriers to compliance.

Trial Locations

Locations (1)

Yale School of Nursing; 🇺🇸 New Haven, Connecticut, United States