Clinical Research Directory

Feasibility and Effects of Noninvasive Brain Stimulation on Pain Perception in People With Fibromyalgia

The goal of this interventional study is to learn whether noninvasive brain stimulation (NIBS) will have an effect on pain perception in people with fibromyalgia. The main questions it aims to answer are: Do repeated sessions of NIBS lead to a reduction in perceived pain? Do repeated sessions of NIBS lead to an improvement in quality of life? Researchers will compare different brain targets to see if effects are different between them. Participants will receive repeated daily sessions of NIBS over 4 weeks with application of pressure pain algometry, and complete various questionnaires.

Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study

Chronic fatiguing illnesses such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Fibromyalgia, and Long COVID are becoming a major global health challenge. They cause severe personal and social strain and have no proven, widely effective treatments. Although these conditions have different names, they share many symptoms: long-lasting fatigue that doesn't improve with rest, worsening of symptoms after activity (post-exertional malaise), difficulties with thinking ("brain fog"), poor sleep, and widespread pain. Increasing evidence shows that these illnesses also share similar underlying biological problems. These include ongoing inflammation, problems with the autonomic nervous system (which controls automatic body functions), poor function of the blood vessels, and reduced energy production in cells. Whole-Body Cryotherapy (WBCT) is emerging as a promising non-drug treatment that may help break these cycles. WBCT involves very short, controlled exposure to extreme cold (around -110°C to -160°C). This triggers a rapid response across the nervous, immune, and metabolic systems. The cold acts as a powerful stimulus, encouraging the body to reset imbalanced systems. A session briefly narrows blood vessels and then causes them to widen again, improving blood flow and supporting healthy vessel function. WBCT also appears to reduce inflammation, lower oxidative stress, and improve parasympathetic ("rest-and-recover") nervous system activity. Early studies in ME/CFS and related conditions are encouraging. Small trials have reported reduced fatigue, clearer thinking, and better autonomic regulation after a course of WBCT sessions, with good safety. Research has also shown changes in blood-brain barrier proteins after WBCT, suggesting it may help repair "leaky" barriers that can drive symptoms in ME/CFS and Long COVID. By acting on inflammation, blood flow, and nervous system balance at the same time, WBCT could offers a scientifically grounded and potentially transformative approach in understanding the mechanism behind observed treatment effect.

Feasibility and Preliminary Effects of an Asynchronous Microlearning Intervention on Fibromyalgia Knowledge Among Primary Health Care Workers

This randomized controlled pilot trial will evaluate the feasibility and preliminary effects of an asynchronous microlearning intervention on fibromyalgia knowledge among Primary Health Care workers. Participants will be randomly assigned in a 1:1 ratio to either a control group receiving evidence-based written educational material on fibromyalgia or an experimental group receiving the same written material plus an approximately 5-minute asynchronous educational microlearning video. Participants will have two weeks to review the assigned educational content. Fibromyalgia knowledge will be assessed using the Fibromyalgia Knowledge Questionnaire (FKQ) at baseline, before randomization, and two weeks later. Trial feasibility will be assessed through recruitment, retention, intervention participation, and assessment completion indicators.

Multisite Transcutaneous Electrical Nerve Stimulation in Fibromyalgia: A Randomized, Double-Blind, Sham-Controlled Crossover Trial Comparing Two Stimulation Modalities

Fibromyalgia is a chronic and multifactorial disorder characterized by widespread musculoskeletal pain, heightened pain sensitivity, fatigue, sleep disturbances, cognitive complaints, and affective symptoms such as anxiety and depression. Despite the availability of pharmacological and non-pharmacological interventions, symptom control often remains suboptimal, and currently available treatments may be associated with limited efficacy or poor tolerability. Consequently, there is a growing need for effective, safe, and personalized non-pharmacological therapeutic approaches. In a previous randomized controlled trial (EXOFIB), we investigated the effects of the Exopulse Mollii Suit, a non-invasive neuromodulation device delivering multisite transcutaneous electrical nerve stimulation (TENS), in patients with fibromyalgia. Using stimulation parameters consisting of a frequency of 20 Hz, a voltage of 20 V, and a pulse width of 55-85 µs, active stimulation was associated with clinically meaningful improvements in pain, fatigue, and quality of life compared with sham stimulation. These findings provided evidence supporting the therapeutic potential of the Exopulse Mollii Suit in the management of fibromyalgia-related symptoms. However, while EXOFIB established the efficacy of active stimulation relative to sham stimulation, it did not address whether alternative stimulation parameter configurations could yield superior clinical outcomes. To date, no randomized crossover study has directly compared different active stimulation settings of the Exopulse Mollii Suit in patients with fibromyalgia. Consequently, the optimal stimulation parameters for maximizing therapeutic benefit in this population remain unknown. The present study has therefore been designed to compare the effects of three stimulation modalities delivered by the Exopulse Mollii Suit, including two active stimulation configurations and one sham stimulation condition. The primary objective is to evaluate and compare their effects on functional disability associated with fibromyalgia, assessed using the Fibromyalgia Impact Questionnaire (FIQ). The inclusion of a sham condition allows assessment of non-specific effects while preserving participant blinding. The stimulation conditions evaluated in this study are: * Condition A (active stimulation): frequency 20 Hz, voltage 20 V, pulse width 55-85 µs; * Condition B (active stimulation): frequency 20 Hz, voltage 20 V, pulse width 100-125 µs; * Condition C (sham stimulation): brief initial active stimulation followed by discontinuation of stimulation after one minute, while maintaining identical device settings, session duration, and study procedures in order to preserve participant blinding. By identifying the most effective stimulation setting, this study aims to optimize the clinical use of the Exopulse Mollii Suit in fibromyalgia and to contribute to the development of more individualized neuromodulation strategies. Ultimately, the findings may improve symptom management, reduce functional disability, and enhance quality of life in patients living with fibromyalgia.

Dietary Strategies for the Treatment of Fibromyalgia in Overweight and Obese Patients

Spontaneous, non-sponsored, interventional, controlled, randomized, parallel-arm clinical study. Primary objective To assess the impact of specific dietary approaches (ketogenic diet, Mediterranean diet, or Mediterranean diet supplemented with GABA-producing probiotics, e.g., Bifidobacterium adolescentis PRL2019) on fibromyalgia (FM) severity-particularly pain, sleep quality, anxiety, and depression-using validated questionnaires in female patients with FM and overweight/class I obesity. Secondary objectives * Evaluate effects on anthropometric measures, metabolic profile, and body composition. * Assess changes in gut microbiota composition and metabolomic analysis. * Measure neurosteroids with positive allosteric activity on GABA-A or NMDA receptors in saliva and/or plasma. * Exploratory pilot sub-study to quantify brain GABA and glutamate levels through magnetic resonance spectroscopy (MRS) in a subset of patients. Methods Participants will be recruited from the Rheumatology Unit outpatient clinics of IRCCS Policlinico San Martino Hospital (Genoa). Eligible subjects will be adult women with FM and overweight/obesity, selected through protocol-defined criteria. Enrollment requires written informed consent. At enrollment (baseline), participants will complete validated questionnaires assessing FM severity (pain, sleep quality, depression, anxiety, bowel function). Data collection will include sociodemographic information, Mediterranean diet adherence through PREDIMED questionnaire, basal metabolic rate, medical and dietary history, smoking status, blood pressure, and recent laboratory results. Stool, blood, and saliva samples will be collected for routine tests, metabolomics, and ELISA-based measurement of neuroactive steroids like cortisol, progesterone, DHEA. Within 7 days T1, results will be reviewed and eligible participants randomized to one of three groups: hypocaloric ketogenic diet, Mediterranean diet, or Mediterranean diet plus probiotics. Individualized dietary plans will be provided with written and verbal instructions. Anthropometric measurements (weight, height, BMI, waist circumference, waist-hip ratio) and body composition via bioelectrical impedance analysis BIA will be recorded at T0, T4, T8, and T12, together with biological sample collection. Pilot MRS sub-study A subset of participants will undergo brain GABA and glutamate assessment through MRI spectroscopy performed on a 3T Siemens - Prisma magnet at the baseline, before dietary treatment and after 4 weeks. Results will be compared with spectra from control subjects screened through medical history to exclude relevant diseases.

Treatment of Fibromyalgia and PTSD With Live and Inactive Vagus Nerve Stimulation With PEPC

Fibromyalgia (FM) pain and PTSD are highly prevalent and comorbid with associated increased risk of negative physical and mental health outcomes, including higher risk for opioid use and suicide. This project is designed to determine the effects of a 4 week trial of a device for pain management \[transauricular nerve stimulation (tAN)\] on pain interference and intensity \[Pain, Enjoyment, and Activity General Scale (PEG)\] and PTSD. The investigators will also examine how this impacts the Veterans by examining heart rate variability (HRV) as a stress response related biomarker. The investigators plan to randomize 180 Veterans (estimate up to 360 enrolled) with co-morbid FM and PTSD across pain integrated care and PTSD sites in this prospective study and compare: 1) active tAN for pain + Prolonged Exposure in Primary Care (PE-PC) and 2) sham tAN + PE-PC. Study includes 4 weeks of randomized treatment and 4 weeks of voluntary open label treatment. Veterans are assessed (self report \& interview measures, heart rate variability by wearable device) at Intake, Baseline/Post Run-In, Week 2, Week 4, Week 8 and 4 month follow-up. The investigators plan to retain data after the study for potential future use in research.

Electroconvulsive Therapy for Refractory Fibromyalgia

This multicenter, prospective, randomized, open-label, wait-list controlled trial will evaluate the efficacy and safety of bilateral electroconvulsive therapy (ECT) for adults with refractory fibromyalgia (FM). Participants will be recruited from Beijing Tiantan Hospital and Beijing Jianjia Rehabilitation Hospital. Eligible participants will have FM diagnosed according to the 2010 American College of Rheumatology criteria, will have received stable standard medical treatment including at least two combined pharmacological treatments during the previous 3 months, and will have substantial disease-related functional impairment as indicated by a Revised Fibromyalgia Impact Questionnaire (FIQR) score of 39 or higher. Concomitant medications will remain at stable doses during the study whenever possible. Participants will be randomized to an immediate ECT group or a wait-list control group. Participants in the immediate group will receive bilateral ECT in addition to their usual standard treatment. ECT will be administered under general anesthesia using a standardized bilateral electrode placement and individualized stimulus dosing, with 1 to 2 treatment sessions per week for a total of 6 sessions over 4 weeks. Participants in the wait-list group will continue usual standard treatment during the initial randomized control period and will subsequently be offered the same 4-week ECT course. The primary outcome is the change in average pain intensity, measured using the 0-10 Numeric Rating Scale (NRS), from baseline to 1 month after completion of the initial 4-week treatment or control period. Secondary outcomes include pain intensity, FM-related functional impairment, sleep quality, depressive symptoms, health-related quality of life, patient-reported global improvement, cognitive function, memory complaints, postictal confusion, and adverse events. Follow-up assessments will continue for 3 months after ECT or the corresponding control period. Outcome assessors and statisticians will be blinded to treatment allocation.

Investigating the Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on the Brain in People With Fibromyalgia

The first goal of this study is to see how brain activity changes in people with fibromyalgia after they get a treatment called rTMS (repetitive transcranial magnetic stimulation). Researchers are looking at how the parts of the brain that control movement (called motor cortices) respond to this treatment. The second goal is to find out if the changes in brain activity are different between the right and left sides of the brain, depending on which side gets the treatment.

Effects of Curcumin-Piperine Supplementation in Fibromyalgia

The goal of this clinical trail is to evaluate the effectiveness and safety of curcumin-piperine supplementation in patients with fibromyalgia over 3 months compared to placebo. Participants will: Be randomly assigned to receive either curcumin and piperine supplements or a placebo. Attend scheduled clinic visits for clinical assessments and blood sample collection. Complete study questionnaires before and after treatment time frame. The primary question the study aim to answer is: Does Curcumin-piperine supplementation reduce pain intensity by Visual Analog Scale (VAS), compared with placebo? The secondary questions this study aims to answer are: Does supplementation improve fibromyalgia disease impact and quality of life? Does supplementation improve inflammatory biomarkers and oxidative stress? Does supplementation improve insulin resistance? Is curcumin and piperine supplementation safe and well tolerated?

The Effect of Fermented Grape Juice Consumption on Fibromyalgia Patients

The goal of this clinical trial is to learn if a traditional grape-based fermented drink called hardaliye helps treat fibromyalgia in adult women. We will also learn whether adding hardaliye to a personalized nutrition plan works better than using either one alone. The main questions are: Does diet + hardaliye improve antioxidant status and lower oxidative stress more than diet only or hardaliye only? Does diet + hardaliye lower inflammation (TNF-α, IL-6, hs-CRP) and raise SIRT1 levels? Do these changes relate to less pain and better symptoms (fibromyalgia impact, gut symptoms, sleep, mood)? Are there benefits for weight, waist size, blood pressure, and blood lipids? How the groups are compared: Researchers will compare three groups for 8 weeks: Diet + Hardaliye (personalized medical nutrition plan + one 200 mL bottle of hardaliye daily) Diet only (personalized medical nutrition plan) Hardaliye only (usual diet + one 200 mL bottle of hardaliye daily) Participants will: Drink one 200 mL bottle of hardaliye each day if assigned to Diet + Hardaliye or Hardaliye only Follow a personalized nutrition plan if assigned to Diet + Hardaliye or Diet only Visit the clinic at the start and end of the study, with brief check-ins around weeks 2, 4, and 6 Give blood samples before and after the 8-week period Complete short questionnaires on pain, fibromyalgia impact, gut symptoms, sleep, and mood Keep simple logs of daily drink intake and diet plan adherence, and report any side effects Who can join: Adult women (20-40 years) with doctor-diagnosed fibromyalgia and BMI 25.0-29.9 kg/m² who meet the study's health and medication criteria.

The Effect of Physiotherapy Integrated With Yoga and Mindfulness on Individuals With Fibromyalgia

The current study investigates the effect of an integrative physiotherapy and mind-body program called PhYoMind intervention on disability and symptoms in individuals with fibromyalgia (FM). Participants will be randomized to either the PhYoMind intervention, which combines specific physiotherapy techniques with yoga and mindfulness, or to a home exercise control group. The intervention lasts 8 weeks, with supervised and home sessions. The primary outcome is disability, with secondary outcomes including measures of central and autonomic nervous system function, pain perception, stress, fatigue, and sleep quality. Adverse events and adherence of the intervention will be also assessed.

Social Media Connectedness in Fibromyalgia

Patients suffering from fibromyalgia commonly experience depressive symptoms such as loneliness and hopelessness due to the nebulousness of the disease. A primary purpose of social media is to promote connectedness, which is associated with improved well-being. Using archival, de-identified data collected by a social media company, this study aims to explore whether connectedness among patients with fibromyalgia facilitated by social media can improve mental and physical health outcomes.

EEG Prediction and Clinical Efficacy of tDCS in Fibromyalgia.

The purpose of this randomized controlled trial is to investigate the non-inferiority, and possible superiority, of a high-dose home-based tDCS protocol compared with a conventional home-based protocol, and to assess its cost-effectiveness, in patients with fibromyalgia. As complementary goals, we aim to assess the predictive value of baseline EEG for clinical response to high-dose home-based tDCS treatment; and to describe the effectiveness of a high-dose home-based protocol applied to the motor cortex (M1) versus the dorsolateral prefrontal cortex (DLFPC) in patients with fibromyalgia.

Pain Neuroscience Education for Chronic Pain

Chronic pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, with a high prevalence in Spain (25.9%) and an average duration of 6.83 years, highlighting its significant health and social impact. Among its manifestations, chronic low back pain (CLBP) is the most common, affecting 58.1% of individuals with chronic pain, while fibromyalgia (FM) accounts for 10.4%. In both cases, a relevant proportion of patients do not present a clear organic cause, which complicates diagnosis and treatment and reflects the complexity of nonspecific chronic pain. CLBP is associated with a high functional and occupational impact, being one of the main causes of temporary disability. FM, on the other hand, is characterized by widespread musculoskeletal pain accompanied by fatigue, sleep disturbances, and emotional symptoms, constituting a condition with systemic involvement. Both conditions can occur throughout the lifespan, with variations in prevalence depending on age, sex, social class, and the presence of comorbidities. Aging introduces relevant differences in pain experience and treatment response. At the physiological level, changes occur in the musculoskeletal system, such as the progressive loss of muscle mass (especially type II fibers) and decreased bone mineral density, which increases the risk of sarcopenia and frailty. In contrast, young adults show greater anabolic capacity, better hypertrophic response, and higher neuromuscular efficiency, favoring faster adaptations to exercise. These differences justify the need to consider age as a key factor in the therapeutic approach. In addition to structural changes, central sensitization plays a fundamental role in the chronification of pain. This process involves sustained hyperexcitability of the central nervous system, with a reduced pain threshold and altered inhibitory mechanisms, contributing to the persistence of pain even in the absence of significant tissue damage. Therapeutic exercise (TE) is one of the main non-pharmacological interventions for chronic pain and has demonstrated effectiveness in reducing pain and improving functionality. However, its long-term effects are limited, largely due to adherence issues related to pain, as well as psychological, social, and educational factors. Educational level influences both the understanding of the intervention and adherence, generally being higher in young adults, which may affect treatment outcomes. In this context, Pain Neuroscience Education (PNE) has emerged as a complementary strategy aimed at improving understanding of pain mechanisms and promoting adaptive behavioral changes. The combination of PNE and TE has shown positive effects in patients with CLBP and FM, especially in variables related to pain and psychosocial factors. However, there is a lack of evidence regarding the impact of this combination on objective functional parameters, such as spinal movement during functional activities. Therefore, it is necessary to investigate the effectiveness of the combined intervention of PNE and TE not only on pain but also on biomechanical variables such as range, velocity, and quality of movement, using precise measurement instruments.

Investigation of Pain Modulation Phenotypes in Female Patients With Fibromyalgia

Fibromyalgia is characterized by altered pain processing, including impaired descending pain inhibition and central sensitization. While both mechanisms have been independently associated with disease severity, their interrelationship remains unclear. This cross-sectional study aims to investigate whether central sensitization symptoms mediate the relationship between conditioned pain modulation and fibromyalgia impact.

AI and Computer Vision-Assisted Telerehabilitation in Fibromyalgia: The FibroIA 2.0 Trial

Fibromyalgia (FM) is a primary chronic pain condition with an estimated prevalence of 3.3% in Chile. It is characterized by widespread musculoskeletal pain, fatigue, and impaired physical function. Although exercise therapy is considered the first-line intervention, barriers to access and poor adherence limit its effectiveness within the public healthcare system. This study evaluates the effectiveness of an Artificial Intelligence (AI)- and Computer Vision (CV)-assisted telerehabilitation platform called Rehbody. The aim is to determine whether real-time technology-driven feedback can overcome the limitations of traditional face-to-face rehabilitation models by improving disease impact and functional capacity in Chilean patients with fibromyalgia.

Interdisciplinary Program to Improve Quality of Life in People With Fibromyalgia

Fibromyalgia is a chronic condition characterized by widespread pain, fatigue, sleep disturbances, and psychological symptoms that significantly affect quality of life. This quasi-experimental study aims to evaluate the effectiveness of the FIBROCatCentral interdisciplinary program in improving health-related quality of life among adults with fibromyalgia receiving care in Primary Care centers in Central Catalonia, Spain. Participants in the intervention group will attend a structured multidisciplinary program consisting of 24 sessions delivered by healthcare professionals from different disciplines, including nursing, medicine, physiotherapy, nutrition, mental health, social work, and pharmacy. Outcomes will be assessed at baseline and at 3, 6, and 12 months. The primary outcome is health-related quality of life measured using the EuroQol-5D questionnaire. Secondary outcomes include fibromyalgia impact, depressive symptoms, treatment adherence, participant satisfaction, and changes in pharmacological treatment.

Interventional Study on the Effects of Forest Therapy in Fibromyalgia Patients

The goal of this clinical trial is to evaluate if Forest therapy can reduce pain levels and improve the quality of life related to the level of pain perceived in fibromyalgia patients. The main question it aims to answer is: Does frequenting certified forest environments, according to the principles and methods of Forest Therapy, produce positive effects on chronic pain and the consumption of painkillers? The study is part of the "Forest Therapy Project as a Broad-Spectrum Tool for Patients Affected by Fibromyalgia" funded by the Tuscany Region as part of the Complementary Medicine program for the three-year period 2025-2027. The project will be carried out thanks to the collaboration with the National Research Council - Institute for BioEconomy (CNR-IBE)

Comorbidity Between Attention Deficit Hyperactivity Disorder and Fibromyalgia

The overall objective of the research project presented here is to assess the prevalence of fibromyalgia in patients being treated for ADHD, the prevalence of ADHD in patients being treated for fibromyalgia, and the neurobiological correlates of ADHD-fibromyalgia comorbidity.

Aerobic Dance Exercises in Fibromyalgia Syndrome

The aim of this study was to evaluate the effects of aerobic dance exercises on patients with Fibromyalgia syndrome (FMS) and to compare these effects with those of conventional postural exercises.

Probiotics for Cognitive Function, Pain, and Quality of Life in People With Fibromyalgia

Fibromyalgia is a complex chronic disorder in which emerging evidence suggests a relevant role of the gut microbiota in modulating physiological processes through the gut-brain axis. In this context, probiotics have been proposed as a potential therapeutic strategy for symptom management in fibromyalgia. This study aimed to evaluate the effects of a multispecies probiotic formulation administered over 12 weeks on pain and fatigue in patients with fibromyalgia. Secondary outcomes included sleep disturbances, cognitive function, and emotional symptoms. This was a quadruple-blinded, randomized, placebo-controlled clinical trial. Participants were randomly assigned to receive either a daily capsule of a multispecies probiotic (Teoliance HPi10, Therascience) containing Lactobacillus acidophilus LA-3, Lactobacillus rhamnosus GG, Bifidobacterium BS01, Lactobacillus plantarum BG112, Streptococcus thermophilus SP4, Lactobacillus casei LCO3, and Lactobacillus reuteri LR92, or placebo, for 12 weeks. Clinical outcomes were assessed using validated questionnaires including VAS, BPI, SF-36, MOS, HADS, and FIQ.

Functional and Affective Effects of a Brief tDCS Intervention in Fibromyalgia and Chronic Fatigue Syndrome

Functional and Affective Effects of a brief tDCS Intervention in Fibromyalgia and Chronic Fatigue Syndrome Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are characterized by persistent, multidimensional symptoms arising from complex brain-body interactions that impair functioning and quality of life. Noninvasive neuromodulation techniques such as transcranial direct current stimulation (tDCS) have been proposed as adjunctive approaches to support short-term functional changes within distributed neural systems, although evidence remains limited and heterogeneous. The objective is to examine immediate pre-post changes in multidimensional clinical outcomes following a standardized tDCS protocol in patients with FM and CFS, and to explore potential diagnosis-related response patterns.

Between Paws and Affections - Impact of Dog-Assisted Therapy in Fibromyalgia Patients

The purpose of this study is to evaluate the effectiveness and medium-term maintenance of a structured dog-assisted therapy (DAT) protocol, "Entre Patas e Afetos" (Between Paws and Affections), in reducing pain, anxiety and depressive symptoms and in improving functional status and quality of life in Portuguese patients with fibromyalgia (FM) followed at ULS Alto Ave, with systematic outcome assessment in the immediate post intervention phase (T2), 6-month follow-up (T3) and 12-month follow-up (T4).

Chronic Fibromyalgia Pain, Lifestyle Factors, and Inflammation

The goal of this observational study is to understand how lifestyle factors (such as diet, physical activity, sleep, stress, smoking, and alcohol intake) predict changes in pain sensitivity and modulation in adults aged 18-65 with chronic fibromyalgia pain. The main questions it aims to answer are: What is the predictive relationship between lifestyle factors and pain sensitivity/modulation? What is the mediating role of inflammation in the relationship between lifestyle factors and pain? Researchers will explore how various lifestyle factors collectively and individually relate to pain responses and whether inflammatory markers (IL-6, TNF-α, IL-10) mediate these associations. Participants will: Wear a Fitbit for two weeks to measure physical activity and sleep Use the Nutritics app to log food intake Complete an online questionnaire on pain, sleep quality, stress, and quality of life Undergo pain sensitivity testing using a digital algometer and pressure cuff Have body weight, height, and BMI measured Provide a blood sample for analysis of inflammatory markers via ELISA