REgulating Pain Through Neurofeedback in infLammatory Bowel diseasE and Musculoskeletal Dysfunction (RELIEF)

Regolazione Del Dolore Tramite Neurofeedback Nelle Malattie Infiammatorie Intestinali e Nelle Disfunzioni Muscoloscheletriche

Clinical trial with a CE-marked medical device. Use as indicated in patients with chronic inflammatory bowel disease and musculoskeletal pain. The aim of this study is to evaluate the efficacy of neurofeedback therapy in managing musculoskeletal pain in patients with chronic inflammatory bowel disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Behavioral: Experimental group; Behavioral: Placebo group

Detailed Description

Clinical trial with a CE-marked medical device. Use as indicated in patients with chronic inflammatory bowel disease and musculoskeletal pain, with the primary objective of evaluating the efficacy of neurofeedback therapy in managing musculoskeletal pain in patients with chronic inflammatory bowel disease.

In addition, psychological and microbiome characteristics will be analyzed in a cohort of adult patients with IBD and joint pain. Subjects will be randomly assigned to two groups in permuted blocks of eight, with a 1:1 ratio. The sequence, generated via a computer algorithm using SAS (Statistical Analysis System) software, will be hidden from investigators to avoid selection bias.

The study will recruit 80 patients: 40 assigned to the clinical group, who will receive eight sessions of alpha/theta neurofeedback, and 40 to the control group, who will receive no psychological treatment.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elisa Foscarini; Phone Number: 0630157103; Email: elisa.foscarini@policlinicogemelli.it
• Study Contact Backup: Name: Francesca Profeta; Email: francesca.profeta@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged between 18 and 65 years.
• Patients diagnosed with IBD for at least six months.
• Ability to understand and provide signed informed consent.
• Patients with IBD and a prior diagnosis of axial/peripheral spondyloarthritis without objective evidence of joint inflammation (clinical and/or instrumental, as per rheumatological assessment), but with persistent musculoskeletal pain (VAS scale score >50/100 in the last week; HAQ-DI score >0.5; FACIT Fatigue Scale score ≥40; NPS score >1)

Or

• Patients with IBD and musculoskeletal pain who do not meet the criteria for the diagnosis of spondyloarthritis or other inflammatory arthritis (as per rheumatological assessment), but with persistent musculoskeletal pain (VAS scale score >5/10 in the last week; HAQ-DI score >0.5; FACIT Fatigue Scale score ≥40; NPS score >1).

Exclusion Criteria:

• Patients under 18 or over 65 years of age.
• Patients affected by Inflammatory Bowel Disease-Unclassified (IBD-U).
• Inability to provide informed consent.
• Refusal to provide informed consent.
• Presence of severe language deficits.
• Patients diagnosed with axial/peripheral spondyloarthritis with objective evidence of joint inflammation (clinical and/or instrumental, as per rheumatological assessment).
• Patients with other comorbidities that may invalidate rheumatological evaluation (Substance Use Disorder, Schizophrenia Spectrum and other Psychotic Disorders, Diabetes Mellitus, other rheumatological diseases).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental treatment; A group of patients will receive the experimental treatment with 8 sessions of alpha/theta neurofeedback (CE marked medical device)	Behavioral: Experimental group; Experimental psychotherapy treatment with 8 sessions of alpha/theta neurofeedback
Placebo Comparator: Control group; Control group that will not receive any psychological treatment with neurofeedback but only psychological support according to the standards of care	Behavioral: Placebo group; Classical psychological treatment according to standards of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in pain intensity measured by the Visual Analog Scale (VAS)	The Visual Analog Scale for Pain ranges from 0 to 100 points, where: 0 = no pain 100 = worst imaginable pain Higher scores indicate greater pain intensity (worse outcome).	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease activity in patients with inflammatory bowel disease	Disease activity will be assessed using standard disease activity indices according to clinical practice (e.g., validated indices specific for inflammatory bowel disease). Scale ranges and interpretation depend on the specific index used; higher scores indicate greater disease activity.	12 weeks
Pain intensity measured by the Visual Analog Scale (VAS)	Pain intensity will also be assessed using the Visual Analog Scale for Pain (VAS), ranging from 0 to 100 points: 0 = no pain 100 = worst imaginable pain Higher scores indicate worse pain.	12 weeks
Health-related quality of life and psychological distress	Health-related quality of life and psychological distress will be assessed using validated questionnaires. Each questionnaire will be reported separately with its defined score range and interpretation according to the respective instrument.	12 weeks
Gut microbiota composition and diversity	Gut microbiota composition and diversity will be assessed through stool sample analysis. Microbial diversity will be evaluated using ecological diversity metrics, including alpha-diversity and beta-diversity indices.	12 weeks
Maintenance of pain reduction measured by the Visual Analog Scale (VAS)	To evaluate whether the reduction in perceived pain achieved at the end of treatment is maintained during follow-up. Pain intensity will be measured using the Visual Analog Scale for Pain (VAS). Range: 0-100 0 = no pain 100 = worst imaginable pain Higher scores indicate worse pain intensity. Pain will be assessed at: Baseline End of treatment (8 weeks) Follow-up (12 weeks after treatment completion)	20 weeks
Functional disability measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI)	Functional disability will be assessed using the Health Assessment Questionnaire - Disability Index (HAQ-DI). Range: 0-3 0 = no disability 3 = severe disability Higher scores indicate worse functional impairment. Assessments will be performed at: Baseline End of treatment (8 weeks) Follow-up (12 weeks after treatment completion)	20 weeks
Fatigue measured by the Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue)	Fatigue will be measured using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue). Range: 0-52 Higher scores indicate less fatigue (better outcome). Assessments will be performed at: Baseline End of treatment (8 weeks) Follow-up (12 weeks after treatment completion)	20 weeks
Neuropathic pain measured by the Neuropathic Pain Scale (NPS)	Neuropathic pain will be assessed using the Neuropathic Pain Scale (NPS). Total score range: 0-100 Higher scores indicate worse neuropathic pain. Assessments will be performed at: Baseline End of treatment (8 weeks) Follow-up (12 weeks after treatment completion)	20 weeks
Pain intensity measured by the Visual Analog Scale (VAS) between intervention and control groups	Pain intensity will be measured using the Visual Analog Scale for Pain (VAS). Range: 0-100 0 = no pain 100 = worst imaginable pain Higher scores indicate worse pain intensity. Pain scores will be compared between the neurofeedback intervention group and the control group receiving no psychological intervention.	12 weeks
Functional disability measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) between intervention and control groups	Functional disability will be measured using the HAQ-DI. Range: 0-3 Higher scores indicate worse disability. Scores will be compared between the neurofeedback intervention group and the control group.	12 weeks
Fatigue measured by the Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) between intervention and control groups	Fatigue will be assessed using the FACIT-Fatigue scale. Range: 0-52 Higher scores indicate less fatigue (better outcome). Scores will be compared between the neurofeedback intervention group and the control group.	12 weeks
Neuropathic pain measured by the Neuropathic Pain Scale (NPS) between intervention and control groups	Neuropathic pain will be assessed using the Neuropathic Pain Scale (NPS). Range: 0-100 Higher scores indicate worse neuropathic pain. Scores will be compared between the neurofeedback intervention group and the control group.	12 weeks
Assessment of Neurofeedback Learning Measured by EEG Theta/Alpha Ratio	Neurofeedback learning will be assessed by measuring changes in the electroencephalographic (EEG) theta/alpha power ratio. The theta/alpha ratio represents the relative spectral power between theta and alpha frequency bands derived from EEG recordings. Measure: Theta/Alpha Ratio derived from EEG recordings. This is a continuous variable representing the ratio between theta-band power and alpha-band power. The measure has no fixed theoretical upper limit. Changes in the ratio reflect modifications in the relative distribution of EEG spectral power between theta and alpha frequency bands. The theta/alpha ratio will be assessed at: Baseline End of treatment (8 weeks) Follow-up (12 weeks after treatment completion) Higher or lower values will be interpreted as changes in neurophysiological activity associated with the neurofeedback training.	20 weeks

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Franco Scaldaferri, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): February 25, 2026
• Primary Completion (Estimated): May 2, 2026
• Study Completion (Estimated): December 2, 2026

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: microbiota; pain management; musculoskeletal pain; psychological evaluation
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Neurobehavioral Manifestations; Gastroenteritis; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Musculoskeletal Pain; Inflammatory Bowel Diseases; Agnosia
• Other Study ID Numbers: RELIEF_7654

Drug and device information, study documents

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