Neuro-modulation of Central Pain Pathways in Non Inflammatory Musculoskeletal Pain Syndrome (NMJFP protocol)
August 21, 2026 updated by: Istituto Giannina Gaslini
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.
Study Overview
Status
Enrolling by invitation
Conditions
Detailed Description
This clinical trial investigates the efficacy and safety of transcranial electrical stimulation (tES) as a non-pharmacological intervention for pain management in pediatric patients (ages 10-21, both sexes) with juvenile fibromyalgia (JFM) and other non-inflammatory musculoskeletal pain syndromes (MPS).
These conditions are characterized by chronic, widespread musculoskeletal pain, fatigue, sleep disturbances, cognitive and psychological symptoms, and significantly reduced quality of life.
Current management strategies are multidisciplinary, but there is no gold standard treatment, especially for pediatric patients.The study is a 24-month, open-label, randomized, actively controlled, mono-center, prospective, superiority trial.
Forty-six participants will be randomly assigned to one of two arms: Active tES or Sham tES.
The primary aim is to determine whether active tES leads to significant improvements in pain (≥30% reduction) and quality of life (≥20% improvement) compared to sham stimulation.
Secondary aims include evaluating changes in neurophysiological markers (such as motor evoked potentials, MEPs) and functional outcomes.Participants will undergo a comprehensive assessment including behavioral, neurophysiological, and patient-reported outcome measures.
Behavioral assessments include quality of life questionnaires (J-FiMAR), physical and motor function tests (6-Minute Walking Test, Shuttle Run, Sit-up, Long Jump, Flamingo Balance Test, Functional Mobility Scale), and patient-reported outcomes (pain, fatigue, sleep, mood).
Neurophysiological assessments involve transcranial magnetic stimulation (TMS) and electromyography (EMG) to measure cortical excitability and MEPs before and after the intervention.The intervention consists of 10 consecutive daily sessions (over 2 weeks) of either active or sham tES.
Active tES is delivered for 20 minutes per session, with the anodal electrode placed over the left primary motor cortex (C3, 10-20 EEG system) and the reference electrode over the contralateral supraorbital region.
Sham tES mimics the initial sensation of stimulation but does not deliver active current after the first minute.
Both protocols use CE-certified, pediatric-appropriate equipment and follow international safety guidelines.Randomization is performed using random permuted blocks via Random.org to ensure balanced group allocation.
The study includes interim analysis after 50% enrollment.
Data analysis will use appropriate statistical methods (t-tests, ANOVA, non-parametric tests, Bonferroni correction) to compare outcomes between groups and assess effect sizes.Risks associated with tES and TMS are minimal, with the most common adverse effects being mild and transient (e.g., headache, tingling).
Strict inclusion/exclusion criteria and continuous monitoring ensure participant safety.
Ethical conduct is maintained according to international guidelines, with informed consent/assent required from all participants and their guardians.The results of this trial will provide valuable evidence on the feasibility, safety, and effectiveness of tES as a pain management strategy in young people with JFM and related conditions.
The study also aims to identify objective neurophysiological and functional markers that could guide future personalized interventions and improve quality of life for affected patients.
Study Type
Interventional
Enrollment (Estimated)
46
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
GE
-
Genova, GE, Italy, 16147
- Ronchetti Anna Bruna
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
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.
Exclusion Criteria: iagnosis of epilepsy or at risk of seizuresPresence of a cardiac pacemakerPresence of an implanted infusion pump, metal plates in the skull, or metal objects in the eye and skull (e.g., after neurosurgical interventions)Past or present history of substance abusePast or present history of neuropsychiatric disorders (major depression and schizophrenia)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Active tES
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
|
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
|
|
Sham Comparator: Sham tES
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
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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)
Time Frame: 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
|
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)
Time Frame: 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
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in multidimensional patient-reported outcomes from baseline to follow-up.
Time Frame: 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
|
The secondary outcome measures in this study are designed to provide a comprehensive evaluation of the impact of transcranial electrical stimulation (tES) on multiple aspects of functioning and well-being in children and adolescents with juvenile fibromyalgia and other non-inflammatory musculoskeletal pain syndromes patient-reported outcomes including fatigue, sleep quality, mood, and cognitive function, as well as physical activity and sedentary behavior patterns.
|
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.
Time Frame: 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.
|
The secondary outcome measures in this study are designed to provide a comprehensive evaluation of the impact of transcranial electrical stimulation (tES) on multiple aspects of functioning and well-being in children and adolescents with juvenile fibromyalgia and other non-inflammatory musculoskeletal pain syndromes in functional and motor performance through standardized tests (6-Minute Walking Test= meters; Shuttle Run= Seconds; Sit-up= number, Long Jump= meters, Flamingo Balance= number, FMS= meters).
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in TMS-derived neurophysiological indices (SICI, ICF, sICF, LICI, IHI, MEP amplitude, time-to-baseline) before and after intervention
Time Frame: 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
|
TMS-derived neurophysiological indices-including SICI, ICF, sICF, LICI, IHI, MEP amplitude, and time-to-baseline-are measured before and after the intervention to objectively assess changes in cortical excitability and connectivity.
These outcomes provide insight into the neurophysiological mechanisms underlying the effects of non-invasive brain stimulation in pediatric patients with non-inflammatory musculoskeletal pain syndromes
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 31, 2025
Primary Completion (Estimated)
March 1, 2027
Study Completion (Estimated)
March 1, 2028
Study Registration Dates
First Submitted
August 21, 2026
First Submitted That Met QC Criteria
August 21, 2026
First Posted (Actual)
August 25, 2026
Study Record Updates
Last Update Posted (Actual)
August 25, 2026
Last Update Submitted That Met QC Criteria
August 21, 2026
Last Verified
August 1, 2026
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRCCS Istituto Giannina Gaslin
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.