Juvenile Fibromyalgia Syndrome (JFS) is a chronic condition affecting children and adolescents, characterised by widespread musculoskeletal pain and a significant impact on daily life and quality of life. Gastrointestinal symptoms and changes in gut microbiota have been reported in patients with fibromyalgia, suggesting a possible role of the gut-immune system interaction in the disease. This study aims to investigate whether Gabapral®, a food supplement containing the probiotic strain Bifidobacterium adolescentis PRL2019, may help reduce pain symptoms and improve clinical outcomes in paediatric patients with JFS. The hypothesis of this study is that modulation of the gut microbiota with Gabapral® may contribute to improvement of symptoms related to Juvenile Fibromyalgia Syndrome.
Juvenile Fibromyalgia Syndrome (JFS) is a complex condition characterised by widespread pain, fatigue, and functional impairment. The pathophysiology of JFS is multifactorial, involving mechanisms related to central sensitisation, pain regulation, immune response, and possible alterations in the gut-brain axis. The intestinal microbiota is involved in several physiological processes, including regulation of immune function, maintenance of intestinal barrier integrity, and production of bioactive metabolites that may influence communication between the gut and nervous system. Alterations in gut microbiota composition have been described in patients with fibromyalgia, and gastrointestinal symptoms are frequently observed in this population. Gabapral® contains Bifidobacterium adolescentis PRL2019, a probiotic strain naturally found in the human intestinal microbiota. Bifidobacterium adolescentis has been associated with immunomodulatory properties and the production of gamma-aminobutyric acid (GABA), a metabolite involved in gut-brain communication. Preclinical studies have identified PRL2019 among strains with high GABA-producing capacity. Previous studies have evaluated the safety and potential effects of Bifidobacterium adolescentis PRL2019 in paediatric patients with gastrointestinal disorders, including irritable bowel syndrome. However, its potential role in Juvenile Fibromyalgia Syndrome has not yet been explored. This study is designed to investigate whether modulation of the gut microbiota through Gabapral® supplementation may influence clinical symptoms and biological pathways associated with JFS. Exploratory microbiota and metabolomic analyses will provide additional information regarding possible mechanisms underlying treatment response.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
Gabapral® is an oral food supplement containing Bifidobacterium adolescentis PRL2019, provided as single-dose oral sticks containing 20 × 10\^9 colony-forming units (CFU). Participants will receive one oral stick once daily for a 12-week treatment period according to the assigned treatment sequence. The product is gluten- and lactose-free.
Matching placebo provided as an oral supplement stick, identical to Gabapral® in appearance, taste, texture, weight, and packaging. The placebo does not contain Bifidobacterium adolescentis PRL2019 or other active microorganisms. Participants will receive one oral stick once daily during the assigned 12-week treatment period.
IRCCS Giannina Gaslini
Genova, Genova, Italy
To evaluate the clinical effectiveness of Gabapral® in reducing musculoskeletal pain in paediatric patients with JFS.
Reduction in musculoskeletal pain intensity, measured by the 21-numbered circle Visual Analogue Scale (VAS)14, where 0 corresponds to "no pain" and 10 to "worst imaginable pain". Baseline is defined as the mean VAS scores recorded over the 7 days preceding the start of each treatment period (i.e. before Period 1 start and before crossover to Period 2). The treatment effect is calculated as the change from baseline to the mean VAS score recorded over the last 7 days of the treatment period. A patient will be defined as a responder if achieving a 3 2 points reduction in the weekly average VAS score from baseline. The VAS will be self-reported by all enrolled patients.
Time frame: From the start of each treatment period (baseline) to the end of the 12-week treatment period
To assess changes in abdominal pain intensity following treatment with Gabapral®
Abdominal pain intensity will be assessed using the 21-numbered circle Visual Analogue Scale (VAS) (0-10, with half-point scores permitted), where higher scores indicate greater symptom severity.
Time frame: Change from baseline to the end of each 12-week treatment period
To assess changes in fatigue intensity following treatment with Gabapral®
To asses change in fatigue intensity from baseline following treatment with Gabapral. Fatigue intensity will be assessed using the 21-numbered circle Visual Analogue Scale (VAS) (0-10, with half-point scores permitted), where higher scores indicate greater symptom severity.
Time frame: Change from baseline to the end of each 12-week treatment period
To assess changes in functional measures following treatment with Gabapral®
These Functional outcomes include functional disability assessed using the Functional Disability Inventory (FDI). The FDI comprises 15 items, each rated on a 5-point Likert scale (0 = no trouble, 4 = impossible), yielding a total score ranging from 0 to 60, with higher scores indicating greater functional disability
Time frame: Change from baseline to the end of each 12-week treatment period
To assess changes in headache intensity following treatment with Gabapral®
Change in headache intensity from baseline following treatment with Gabapral. Headache intensity will be assessed using the 21-numbered circle Visual Analogue Scale (VAS) (0-10, with half-point scores permitted), where higher scores indicate greater symptom severity.
Time frame: From the start of each treatment period (baseline) to the end of the 12-week treatment period
To assess changes in global assessment of disease severity following treatment with Gabapral®
Change in global assessment of disease severity from baseline following treatment with Gabapral. Global disease severity will be assessed using the 21-numbered circle Visual Analogue Scale (VAS) (0-10, with half-point scores permitted), where higher scores indicate greater symptom severity.
Time frame: From the start of each treatment period (baseline) to the end of the 12-week treatment period
To assess changes in widespread pain following treatment with Gabapral®
Change in widespread pain from baseline following treatment with Gabapral. Widespread pain will be assessed using the Widespread Pain Index (WPI) (0-19), where higher scores indicate greater widespread pain.
Time frame: From the start of each treatment period (baseline) to the end of the 12-week treatment period
To assess changes in symptom severity following treatment with Gabapral®
Change in symptom severity from baseline following treatment with Gabapral. Symptom severity will be assessed using the Symptom Severity Score (SSS) (0-12), where higher scores indicate greater symptom severity.
Time frame: From the start of each treatment period (baseline) to the end of the 12-week treatment period
To assess changes in depressive symptoms following treatment with Gabapral®.
Change in depressive symptoms from baseline following treatment with Gabapral. Depressive symptoms will be assessed using validated instruments, including the Children's Depression Inventory - Second Edition (CDI-2) (0-56) or the Beck Depression Inventory - Second Edition (BDI-II) (0-63). Higher scores indicate greater depressive symptom severity. Scoring will follow the standardized procedures defined in the respective manuals.
Time frame: Change from baseline to the end of each 12-week treatment period
To assess changes in anxiety symptoms following treatment with Gabapral®
Change in anxiety symptoms from baseline following treatment with Gabapral. Anxiety symptoms will be assessed using validated instruments, including the Multidimensional Anxiety Scale for Children - Second Edition (MASC-2) (0-150) or the State-Trait Anxiety Inventory for Youth (STAI-Y) (20-80 for each subscale). Higher scores indicate greater anxiety symptom severity. Scoring will follow the standardized procedures defined in the respective manuals.
Time frame: Change from baseline to the end of each 12-week treatment period
To characterise the composition of the gut microbiota in a cohort of JFS patients.
Gut microbiota composition will be characterised from fecal samples collected before and after each treatment period using shotgun metagenomic sequencing. Results will be reported as the relative abundance of bacterial taxa at the phylum, genus, and species levels together with alpha- and beta-diversity metrics, summarized descriptively at each study time point.
Time frame: Baseline before Period 1 (Week 0), end of Treatment Period 1 (Week 12), baseline before Period 2 following washout (Week 18), and end of Treatment Period 2 (Week 30).
To examine the impact of Gabapral on gut microbiota composition and related metabolomic pathways.
Changes from baseline in gut microbiota taxonomic composition and diversity, determined by shotgun metagenomic sequencing of fecal samples, and in fecal and plasma metabolomic profiles, determined by untargeted metabolomic analysis, will be evaluated after each treatment period. Metabolomic results will be summarised as differential metabolite abundances (up- and down-regulated metabolites) together with pathway enrichment analyses to identify biological pathways associated with treatment response.
Time frame: Baseline (Week 0) and end of each 12-week treatment period (Week 12 and Week 30).
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