Neuro-modulation of Central Pain Pathways in Non Inflammatory Musculoskeletal Pain Syndrome

NCT07785362 | Enrolling By Invitation

• 1 other identifier: IRCCS Istituto Giannina Gaslin
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this clinical trial is to see if transcranial electrical stimulation (tES) can help reduce pain and improve quality of life in children and adolescents (ages 10-21, both sexes) with juvenile fibromyalgia or other non-inflammatory musculoskeletal pain syndromes. The main questions are whether active tES works better than sham (placebo) stimulation for pain relief and whether it leads to measurable changes in brain activity.Participants will be randomly assigned to receive either active or sham tES for 20 minutes a day over two weeks. They'll complete questionnaires about their pain and quality of life, do some simple physical and motor tests, and undergo non-invasive brain measurements before and after the intervention. The results will help understand if tES is a safe and effective option for managing chronic pain in young people. Specific Aims: Aim 1a. transcranial stimulation will be associated with significant improvements in pain and functioning (e.g., 30% or greater symptom relief or 20% or greater improvement in QoL) Aim 1b. For each tES condition, estimate mean changes in motor evoked potential (MEP) amplitudes induced by TMS stimulation. Aim 2. Compare the tES conditions (Active, Sham) in terms of the mean changes in MEP amplitude. Aim 3. Obtain statistical estimates of variance components needed for the planning of a future study. Therefore, we hypothesize that anodal tES stimulation decreases MEP amplitudes compared to sham tES condition. We further hypothesize that MEP amplitudes are positively correlated. This study will be the first randomized, double-blind, controlled study of tES technology in children as an adjunctive pain management strategy for MPS. Data from this trial will likely yield information regarding the feasibility and efficacy of tES as a chronic pain-management approach.

Conditions

Pain Syndrome; Fibromyalgia; CRPS (Complex Regional Pain Syndromes); Neuromodulation; Juvenile; Physical Disability; Physical Inactivity

Keywords

Pain syndrome, Fibromyalgia, Complex regional Pain Syndrome, Neuromodulation, Juvenile, Physical Disability, Physical Inactivity

Outcome Measures

Primary Outcomes (2)

• Change in Pain Intensity from Baseline to Post-Intervention in Pediatric Patients with Non-Inflammatory Musculoskeletal Pain Syndromes Treated with Non Invasive Brain Stimulation (NIBS)

  The primary purpose of this study is to evaluate whether non-invasive brain stimulation (NIBS), specifically transcranial electrical stimulation (tES), can significantly reduce pain in children and adolescents with juvenile fibromyalgia or other non-inflammatory musculoskeletal pain syndromes. The intervention aims to modulate brain circuits involved in pain perception using safe, non-pharmacological techniques. Changes in pain (30% or greater symptom relief, misured by Visual analogue scale - 0= worse/10= better) will be measured before and after treatment, comparing active and sham stimulation groups.

  Primary outcomes will be assessed at four time points: before the first tES session (baseline), immediately after the last session (post-intervention, after 2 weeks), and at 1 month and 3 months after

• Change in Health-Related Quality of Life from Baseline to Post-Intervention in Pediatric Patients with Non-Inflammatory Musculoskeletal Pain Syndromes Treated with Non Invasive Brain Stimulation (NIBS)

  The primary purpose of this study is to evaluate whether non-invasive brain stimulation (NIBS), specifically transcranial electrical stimulation (tES), can significantly reduce pain in children and adolescents with juvenile fibromyalgia or other non-inflammatory musculoskeletal pain syndromes. The intervention aims to modulate brain circuits involved in pain perception using safe, non-pharmacological techniques. Changes in QoL quality of life (20% or greater improvement in QoL, misured by Visual analogue scale - 0= worse/10= better) will be measured before and after treatment, comparing active and sham stimulation groups.

  Primary outcomes will be assessed at four time points: before the first tES session (baseline), immediately after the last session (post-intervention, after 2 weeks), and at 1 month and 3 months after

Secondary Outcomes (2)

• Change in multidimensional patient-reported outcomes from baseline to follow-up.

  Secondary outcomes will be assessed at four time points: before the first tES session (baseline), immediately after the last session (post-intervention, after 2 weeks), and at 1 month and 3 months after

• Change in functional and motor performance from baseline to follow-up.

  Secondary outcomes will be assessed at four time points: before the first tES session (baseline), immediately after the last session (post-intervention, after 2 weeks), and at 1 month and 3 months after.

Other Outcomes (1)

• Change in TMS-derived neurophysiological indices (SICI, ICF, sICF, LICI, IHI, MEP amplitude, time-to-baseline) before and after intervention

  Others outcomes will be assessed at four time points: before the first tES session (baseline), immediately after the last session (post-intervention, after 2 weeks), and at 1 month and 3 months after

Study Arms (2)

Active tES

ACTIVE COMPARATOR

Active tES (transcranial electrical stimulation) is a non-invasive brain stimulation technique that involves applying a low-intensity electrical current (up to 2 mA) to specific areas of the cerebral cortex through electrodes placed on the scalp. In this study, the active tES protocol delivers current for 20 minutes per session, over 10 consecutive days (2 weeks), with the anodal electrode placed over the left primary motor cortex (C3 position, according to the 10-20 EEG system) and the reference electrode over the contralateral supraorbital region. The goal is to modulate cortical excitability and reduce pain in patients with juvenile fibromyalgia or other non-inflammatory musculoskeletal pain syndromes. The procedure is safe, well-tolerated, and monitored for adverse effects

Other: Neuro-modulation of central pain pathways in non inflammatory musculoskeletal pain syndrome (NMJFP)

Sham tES

SHAM COMPARATOR

Sham tES (transcranial electrical stimulation) is a placebo-controlled procedure designed to mimic the experience of active tES without delivering a sustained electrical current. In this study, for the sham protocol, electrodes are placed in the same positions as for active stimulation. After an initial ramp-up period of 30 seconds, the stimulation fades out over the next 30 seconds, so participants feel the initial tingling sensation but receive no active current for the remainder of the session. At the end of the sham session, stimulation fades in again for 30 seconds and then ends with a final 30-second ramp-down. This method reliably simulates the sensations of active tES and helps reduce expectation bias, while ensuring that no actual neuromodulatory effect is delivered

Other: Neuro-modulation of central pain pathways in non inflammatory musculoskeletal pain syndrome (NMJFP)

Interventions

Neuro-modulation of central pain pathways in non inflammatory musculoskeletal pain syndrome (NMJFP) OTHER

Transcranial electrical stimulation (tES) is a non-invasive neuromodulation technique used in this study to investigate its effects on central pain processing in pediatric patients with juvenile fibromyalgia and other non-inflammatory musculoskeletal pain syndromes. The intervention is integrated within a multidisciplinary approach that combines behavioral assessments, neurophysiological measurements, and quality of life evaluations. The study aims to assess the impact of tES on pain reduction, functional improvement, and neurophysiological markers, while ensuring safety and tolerability in a young population. The intervention is delivered using CE-certified equipment and follows international safety guidelines

Active tES; Sham tES

Eligibility Criteria

• Age: 10 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects aged between 10 and 21 years.Patients with fibromyalgia according to the 1990 criteria of the American College of Rheumatology or Patients with other types of non-inflammatory musculoskeletal pain syndromes.Patients who reported a mean pain score \> 4 on a 10-point visual analog scale (VAS) during the two weeks preceding the clinical trial.Disease duration for more than 6 months, no change in drug treatments during the last month, and lack of response to conventional treatments.

Sponsors & Collaborators

• Istituto Giannina Gaslini: lead

Study Sites (1)

Ronchetti Anna Bruna

Genova, GE, 16147, Italy

Location

MeSH Terms

Conditions

Somatoform Disorders; Fibromyalgia; Complex Regional Pain Syndromes; Sedentary Behavior

Condition Hierarchy (Ancestors)

Mental Disorders; Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Autonomic Nervous System Diseases; Peripheral Nervous System Diseases; Behavior

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: no masking is applied
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a 24-month, open-label, randomized, actively controlled, mono-center, prospective, superiority clinical trial.Randomized: Participants are assigned randomly to treatment groups.Controlled: There is a control (sham) group receiving placebo stimulation.Prospective: Data are collected forward in time from enrollment.Superiority: The study aims to show that active stimulation is superior to placebo.Mono-center: Conducted at a single center (IRCCS G. Gaslini).Open-label: Both researchers and participants know the assigned treatment.

Study Record Dates

• First Submitted: August 21, 2026
• First Posted: August 25, 2026
• Study Start: March 31, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: August 25, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)