PRL2019 in the Treatment of Juvenile Fibromyalgia

Официальное название

A Prospective, Randomised, Controlled Crossover Study on the Effectiveness of Bifidobacterium Adolescentis PRL2019 in the Treatment of Juvenile Fibromyalgia

Обзор

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.

Подробное описание

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.

Вмешательства

• Пищевая добавка Bifidobacterium adolescentis PRL2019
  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.
• Пищевая добавка Placebo
  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.

Первичные конечные точки

• To evaluate the clinical effectiveness of Gabapral® in reducing musculoskeletal pain in paediatric patients with JFS. [Срок оценки: From the start of each treatment period (baseline) to the end of the 12-week treatment period]

Вторичные конечные точки (11)

• To assess changes in abdominal pain intensity following treatment with Gabapral® [Срок оценки: Change from baseline to the end of each 12-week treatment period]
• To assess changes in fatigue intensity following treatment with Gabapral® [Срок оценки: Change from baseline to the end of each 12-week treatment period]
• To assess changes in functional measures following treatment with Gabapral® [Срок оценки: Change from baseline to the end of each 12-week treatment period]
• To assess changes in headache intensity following treatment with Gabapral® [Срок оценки: 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® [Срок оценки: 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® [Срок оценки: 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® [Срок оценки: 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®. [Срок оценки: Change from baseline to the end of each 12-week treatment period]
• To assess changes in anxiety symptoms following treatment with Gabapral® [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: Baseline (Week 0) and end of each 12-week treatment period (Week 12 and Week 30).]

Критерии участия

Критерии включения

• Patients aged between 9 and 25 years;
• Written informed consent to participate in the study obtained prior to the start of the study from the patient or both parents/legal guardians of the patient if a minor, and the assent of the minor;
• Diagnosis of JFS according to the 2010 American College of Rheumatology (ACR) criteria 15, with disease onset before 18 years of age;
• Willingness to comply with follow-up visits and provide biological samples (blood and stool) according to the schedule defined in the protocol.

Критерии исключения

• any conditions that may affect the ability to complete informed consent;
• denial of the informed consent;
• presence of concomitant organic GI diseases, such as inflammatory bowel disease, celiac disease, eosinophilic or autoimmune gastroenteropathies, or history of major abdominal surgery;
• acute infection at the time of recruitment;
• antibiotic treatment within 3 months prior to recruitment;
• use of any prebiotic, probiotic, or postbiotic in the previous 2 months before enrolment;
• significant eating disorders, including diagnosed eating behaviour disorders.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Италия · 1 центр

• IRCCS Giannina Gaslini — Genova

Публикации

• Ting TV, Barnett K, Lynch-Jordan A, Whitacre C, Henrickson M, Kashikar-Zuck S. 2010 American College of Rheumatology Adult Fibromyalgia Criteria for Use in an Adolescent Female Population with Juvenile Fibromyalgia. J Pediatr. 2016 Feb;169:181-7.e1. doi: 10.1016/j.jpeds.2015.10.011. Epub 2015 Nov 3. PMID 26545727
• Giorgio V, Quatrale G, Mennini M, Piccirillo M, Furio S, Stella G, Ferretti A, Parisi P, Evangelisti M, Felici E, Quitadamo P, Di Nardo G. Bifidobacterium adolescentis PRL2019 in Pediatric Irritable Bowel Syndrome: A Multicentric, Randomized, Double-Blind, Placebo-Controlled Trial. Microorganisms. 2025 Mar 10;13(3):627. doi: 10.3390/microorganisms13030627. PMID 40142519
• Duranti S, Ruiz L, Lugli GA, Tames H, Milani C, Mancabelli L, Mancino W, Longhi G, Carnevali L, Sgoifo A, Margolles A, Ventura M, Ruas-Madiedo P, Turroni F. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA. Sci Rep. 2020 Aug 24;10(1):14112. doi: 10.1038/s41598-020-70986-z. PMID 32839473
• Aslan CIn NN, Acik M, TertemIz OF, Aktan C, Akcali DT, Cakiroglu FP, OzcelIk AO. Effect of prebiotic and probiotic supplementation on reduced pain in patients with fibromyalgia syndrome: a double-blind, placebo-controlled randomized clinical trial. Psychol Health Med. 2024 Mar;29(3):528-541. doi: 10.1080/13548506.2023.2216464. Epub 2023 May 24. PMID 37224267
• Roman P, Estevez AF, Miras A, Sanchez-Labraca N, Canadas F, Vivas AB, Cardona D. A Pilot Randomized Controlled Trial to Explore Cognitive and Emotional Effects of Probiotics in Fibromyalgia. Sci Rep. 2018 Jul 19;8(1):10965. doi: 10.1038/s41598-018-29388-5. PMID 30026567
• Garofalo C, Cristiani CM, Ilari S, Passacatini LC, Malafoglia V, Viglietto G, Maiuolo J, Oppedisano F, Palma E, Tomino C, Raffaeli W, Mollace V, Muscoli C. Fibromyalgia and Irritable Bowel Syndrome Interaction: A Possible Role for Gut Microbiota and Gut-Brain Axis. Biomedicines. 2023 Jun 13;11(6):1701. doi: 10.3390/biomedicines11061701. PMID 37371796
• Lavarello C, Ancona S, Malattia C. Juvenile Primary Fibromyalgia Syndrome: Advances in Etiopathogenesis, Clinical Assessment and Treatment: A Narrative Review. Biomedicines. 2025 May 10;13(5):1168. doi: 10.3390/biomedicines13051168. PMID 40426996

Идентификаторы

NCT: NCT07738926 · IGG-microbiotaFMG

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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