Clinical Research Directory

A Multicenter, Randomized, Double-Blind Study on the Efficacy and Safety of Tongluo Kaibi Tablets in the Treatment of Fibromyalgia Syndrome

Fibromyalgia is a chronic, disabling musculoskeletal pain disorder. Pregabalin is the sole pharmaceutical agent approved for the treatment of fibromyalgia in China. Tongluo Kaibi Tablet, an approved proprietary Chinese medicine with collaterals-dredging and blood-activating effects, has demonstrated potential therapeutic benefits for fibromyalgia in preliminary small-scale observational studies, yet high-quality large-sample clinical evidence remains lacking. This multicenter, randomized, double-blind, double-dummy parallel-controlled clinical trial was conducted to evaluate the clinical efficacy and safety of Tongluo Kaibi Tablet in patients with fibromyalgia syndrome.

Transcutaneous Vagus Nerve Stimulation for Pain and Autonomic Dysfunction in Fibromyalgia (RESET-FMS)

Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by widespread pain, fatigue, sleep disturbances, cognitive symptoms, and autonomic dysfunction, significantly impairing quality of life. Increasing evidence suggests that, beyond central pain dysregulation, patients with FMS frequently exhibit autonomic nervous system dysfunction, characterized by sympathetic nervous system (SNS) hyperactivity at rest, with reduced SNS recruitment during orthostatic challenge. Moreover, approximately 50% of patients with FMS show reduced intraepidermal small fiber density on skin biopsy, a condition referred to as small fiber pathology (SFP), which has recently been suggested to contribute to autonomic dysfunction in these patients. Despite currently available pharmacological and non-pharmacological treatments, therapeutic efficacy remains limited, highlighting the need for novel mechanism-based interventions. Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive neuromodulation technique that enhances parasympathetic activity through stimulation of the auricular branch of the vagus nerve. Preliminary studies suggest that tVNS may improve pain, autonomic symptoms, mood, and quality of life in patients with FMS, although available evidence is limited by small sample sizes and heterogeneous methodologies. The RESET-FMS study is a randomized, sham-controlled, double-blind clinical trial designed to evaluate the efficacy of tVNS in patients with FMS. Participants will be randomized in a 1:1 ratio to receive either active tVNS or sham stimulation for four consecutive weeks. Stimulation will be administered daily for 30 minutes using the Nurosym™ device applied at the tragus of the external ear. The primary objective is to assess the effect of active tVNS compared with sham stimulation on fibromyalgia severity, measured by the revised Fibromyalgia Impact Questionnaire (rFIQ) at the end of treatment (T4), adjusted for baseline values. Exploratory objectives include: * evaluation of autonomic symptoms, fatigue, pain distribution, symptom severity, and sleep quality using validated clinical scales, including the Composite Autonomic Symptom Score (COMPASS-31), Fatigue Severity Scale (FSS), Widespread Pain Index (WPI), Symptom Severity Score (SSS), and Pittsburgh Sleep Quality Index (PSQI) at T4; * assessment of the persistence of treatment effects four weeks after treatment discontinuation (T8); * evaluation of treatment effects during intermediate assessments (T2); * evaluation of the effects of tVNS on non-invasive indices of autonomic nervous system function, including heart rate variability (HRV) and sudomotor function assessed by dynamic sweat test (DST); * analysis of serum biomarkers potentially associated with autonomic dysfunction, neuroinflammation, and cognitive symptoms, including neuropeptide Y (NPY), interleukin-6 (IL-6), and neurofilament light chain (NFL); * comparison of treatment response between patients with and without evidence of small-fiber pathology on skin biopsy; * identification of clinical and biological predictors of response to tVNS. The study is expected to provide clinically relevant evidence regarding the efficacy and safety of tVNS in FMS and to improve the understanding of the relationship between pain modulation, autonomic dysfunction, and peripheral nervous system involvement in this condition. The identification of predictors of treatment response may contribute to the development of more personalized therapeutic strategies for patients with FMS.

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.

Auricular Acupuncture for Autonomic Balance and Pain in Fibromyalgia

This longitudinal study evaluates the effects of semi-permanent auricular acupuncture on the Autonomic Nervous System (ANS) activity and pressure pain threshold in adult female patients (aged 35-64) diagnosed with Fibromyalgia according to the 2016 American College of Rheumatology (ACR) criteria. The study aims to investigate how a 5-week treatment cycle influences cardiac autonomic regulation and pain sensitivity

Pain & Reward Neuromodulation of CNS Circuits

This pilot feasibility study aims to evaluate transcranial magnetic stimulation (TMS) targeting the prefrontal cortex in patients with fibromyalgia syndrome (FMS). The study will assess preliminary efficacy and mechanisms of central nervous system changes using neuroimaging, behavioral tasks, sensory testing, and neuroimmune markers. Participants will undergo MRI scans, multi-day TMS sessions, and complete questionnaires. The goal is to generate pilot data for future trials on neuromodulation for chronic pain.

Unilateral and Bilateral taVNS in Fibromyalgia

This randomized controlled trial aimed to compare the effects of unilateral (left-sided) and bilateral transcutaneous auricular vagus nerve stimulation (taVNS) combined with a home exercise program on clinical outcomes, autonomic nervous system function, and exercise performance in individuals with fibromyalgia syndrome (FMS). Participants diagnosed with fibromyalgia were randomly assigned to one of three groups: unilateral taVNS, bilateral taVNS, or a home exercise program. The intervention period lasted two weeks and included ten treatment sessions. Clinical outcomes were assessed using validated scales including the Fibromyalgia Impact Questionnaire (FIQ), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Pittsburgh Sleep Quality Index (PSQI). Autonomic function was evaluated using heart rate variability (HRV) parameters, and exercise performance was assessed based on repetition capacity. The study aimed to determine whether bilateral stimulation provides additional benefits compared to unilateral stimulation and exercise alone. The findings may contribute to understanding the role of neuromodulation strategies in improving autonomic regulation, symptom severity, and functional performance in individuals with fibromyalgia.

Effectiveness of Pain Science Education in Patients With Fibromyalgia Syndrome Living in Rural Areas.

Fibromyalgia Syndrome (FMS) is a complex chronic pain disorder characterized by widespread pain associated with numerous symptoms. It is more common in women over 50 years of age with low educational and socioeconomic status living in rural areas. Pain Science Education (PSE) is one of the most widely used treatments for chronic pain management. This treatment consists of an educational intervention aimed at reconceptualizing and modifying erroneous cognitions regarding pain in these patients. The objective of this study is to evaluate the effectiveness of PSE in patients with FMS living in rural areas. They will be randomly assigned to one of two treatment groups. The intervention group will receive two adapted in-person sessions (90 minutes per session/week) by a therapist experienced in teaching PSE. The control group will begin the conventional treatment they received before participating in the study. After the end of the study, patients in the control group will be given their intervention group records. The variables measured will include the impact of FMS on daily life, pain sensitivity, central sensitization, pain catastrophizing, fear of movement, anxiety and depression, self-efficacy, and assessment of knowledge and beliefs about PSE. Assessments will be conducted before the intervention, after the second PSE session, and three months later by the same researcher.

Craniovertebral Angle and Fibromyalgia Severity

Forward Head Posture Frequency in Fibromyalgia Patients Assessed by Craniovertebral Angle: Association with Symptom Severity. Forward head posture is more common in patients with fibromyalgia and is a factor that increases symptom severity.

Effects of 2-Aticyto Complex and D-Ribose on Pain and Clinical Course in Patients With Fibromyalgia

This multicenter, randomized, double-blind, placebo-controlled study will evaluate whether an oral supplement containing 2-Aticyto Complex and D-ribose (FibroThol), added to ongoing standard medical treatment, improves pain, symptoms, and clinical course in adults with fibromyalgia syndrome. Eligible participants are adults aged 18 to 65 years who have had fibromyalgia for at least 1 year and have been receiving pregabalin and/or duloxetine for at least 3 months. Participants will be randomly assigned to receive either FibroThol or placebo, administered as 15 mL three times daily for 4 weeks, while continuing their existing treatment. Follow-up assessments will be performed at baseline, week 2, and week 4 using patient-reported symptom and function measures. The study aims to determine whether this supportive supplement provides additional benefit compared with placebo in patients with persistent symptoms despite standard therapy.

Metformin for Fibromyalgia Symptoms (INFORM Trial)

The main purpose of the project is to evaluate the safety and efficacy of low dose metformin for improving symptoms associated with fibromyalgia syndrome (FMS) via modulating neuroinflammatory pathways. The investigators hypothesize that FMS patients in the low-dose metformin conditions will show greater improvement in FMS symptoms than those who are in the placebo group. Further, the investigators hypothesize that metformin will increase phosphorylated AMPK in peripheral immune cells of FMS patients and will decrease the transcription of mTORC1, NLRP3 inflammasome, and nociceptive cytokines interleukin 1beta and interleukin 18.

Slow Breathing and Resistance Exercise in Fibromyalgia

This randomized controlled trial investigates whether slow breathing techniques influence heart rate variability, exercise self-efficacy, and resistance exercise performance in women with fibromyalgia. Participants will be randomly assigned to one of three breathing conditions (slow breathing with visual pacer, slow breathing without pacer, or spontaneous breathing) before performing a biceps curl resistance exercise. The study will examine how breathing patterns interact with psychological variables (anxiety sensitivity, pain catastrophizing, pain hypervigilance, and kinesiophobia) to affect physiological and performance outcomes.

Validity, Reliability, and Clinical Correlates of Immersive Virtual Reality Adaptation of the Five Times Sit-to-stand Test and Timed up and go Tests in Women With Fibromyalgia Syndrome

Fibromyalgia syndrome (FMS) is a chronic rheumatic condition characterized by widespread pain, fatigue, and functional impairments that negatively affect physical activity levels, muscle strength, balance, and functional mobility. These impairments may lead to reduced functional capacity and increased sedentary behavior. Therefore, objective assessment of mobility, balance, and functional performance is essential in individuals with FMS. Performance-based tests such as the Five Times Sit-to-Stand Test (5xSTS) and the Timed Up and Go (TUG) test are commonly used to evaluate lower extremity muscle function, balance, and functional mobility due to their simplicity, feasibility, and clinical relevance. Recently, virtual reality (VR)-based assessment methods have emerged as a standardized and objective approach for evaluating functional performance. This study aims to investigate the feasibility and measurement properties of virtual reality-based adaptations of the 5xSTS and TUG tests in individuals with fibromyalgia syndrome using a head-mounted VR system. Findings from this study are expected to contribute to the clinical use of VR technology in mobility and balance assessment in individuals with FMS.

Fibromyalgia Disease Burden in Mothers of Children With Attention-Deficit/Hyperactivity Disorder

In this study, the investigators aimed to evaluate the impact of having a child diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD) on parental disease burden in mothers diagnosed with Fibromyalgia Syndrome (FMS). The study will include 50 mothers with FMS who have a child diagnosed with ADHD and 50 mothers with FMS who have children without any psychiatric disorders. Among mothers of children followed with a diagnosis of ADHD at the Child and Adolescent Psychiatry Outpatient Clinic of Edirne Sultan 1st Murat State Hospital, the presence of widespread body pain will be assessed. Mothers reporting widespread body pain will be referred to the Pain Management Outpatient Clinic of the same hospital for further evaluation for FMS. Mothers diagnosed with FMS will be included in the study group. The comparison group will consist of mothers with FMS who have children without any psychiatric disorders. These participants will be selected from patients diagnosed with FMS who present to the Pain Management Outpatient Clinic of Edirne Sultan 1st Murat State Hospital.

Effectiveness of AI-Guided Exercise and Pain Neuroscience Education for Fibromyalgia (FIBROIA)

This randomized controlled trial will evaluate the effectiveness of a 12-week, home-based telerehabilitation program for adults with fibromyalgia (FM) combining AI-guided exercise with Pain Neuroscience Education (PNE). Fifty participants will be randomized (1:1) to the digital intervention or usual care. The primary outcome is change in pain intensity from baseline to post-intervention (week 13 ± 7 days), with secondary outcomes including physical function and health-related quality of life. Outcome assessors, the principal investigator, and the study statistician will be blinded to group allocation until database lock.

Investigation of the Relationship Between Central Sensitization and Balance in Fibromyalgia

The aim of the study is to investigate the relationship between central sensitization parameters and changes in static and dynamic balance in patients with fibromyalgia. The main questions it aims to answer are: * Do central sensitization parameters differ in patients with fibromyalgia compared to healthy individuals? * How is balance performance in these individuals compared to healthy controls? * Do central sensitization parameters affect static and dynamic balance in patients with fibromyalgia? * Do central sensitization parameters lead to quantitative changes in balance in patients with fibromyalgia?

Shiatsu for Chronic Non-Inflammatory Pain in Children and Adolescents

The goal of this clinical trial is to learn if adding Shiatsu therapy to standard treatment can improve quality of life in children and adolescents with chronic pain that is not caused by inflammation. The main question it aims to answer is: Does Shiatsu therapy help improve the quality of life in children with long-lasting pain? All participants will continue their regular treatment and will also: * Receive a 30-minute Shiatsu session once a week for six weeks * Complete questionnaires about their quality of life and family impact before, during, and after the treatment period The study includes about 40 participants between the ages of 10 and 18, who are already being followed at the pediatric pain and rheumatology clinics at Tel Aviv Sourasky Medical Center.

FIBROmyalgia: Somatic Tracking and Exercise Program Study

The goal of this clinical trial is to learn if the combination of two interventions is more effective in treating fibromyalgia symptoms than one intervention alone. The participant group will be people with fibromyalgia in age group 18-65 years. The two interventions to be tested over sixteen weeks are: * weekly exercise sessions in groups * weekly consultations with a therapist The main question it aims to answer is: Is the combination of group exercising and somatic tracking work more efficient than physical activity alone in terms of managing fibromyalgia? Participants will wear Fitbit activity trackers, register pain intensity daily on a mobile app, and answer the Fibromyalgia Impact Questionnaire (FIQ). They will be divided into four groups: * one group receiving the exercise intervention * one group receiving the psychological intervention * one group receiving both intervention * one control group recieving general physical activity recommendations Before the sixteen weeks intervention period, there will be a baseline period of eight weeks. Durng the baseline period, participants will wear activity trackers and maintain their usual lifestyle. Researchers will compare the combination of the interventions against only one intervention and the control group.

Metabolomic Profiling Based on Nuclear Magnetic Resonance in Fibromyalgia Patients

Evaluation of sera of fibromyalgia patients in terms of energy metabolism function and possible alterations in metabolism predisposing to various degenerative/proliferative diseases.

Arm Exercise Capacity, Muscle Strength and Activities of Daily Living in Patients with Fibromyalgia Syndrome

The aim of this study is to compare the upper extremity exercise capacity, muscle strength and activities of daily living of patients with fibromyalgia syndrome and healthy individuals.

TDCS and Tele-rehabilitation Exercise in Fibromyalgia

This randomized controlled trial aims to analyze the effects of anodal tDCS applied over the primary motor cortex and dorsolateral prefrontal cortex combined with a tele-rehabilitation exercise program in patients with fibromyalgia. The study will compare these effects with each other and with placebo tDCS on the following variables: pain intensity, pain mechanosensitivity, quality of life, fatigue, anxiety, depression, sleep quality, pain catastrophizing, functional capacity, isometric strength, and exercise adherence. Secondary objectives include: * Describing the sociodemographic, clinical, and functional characteristics of fibromyalgia patients. * Comparing exercise intensity levels between patients receiving tDCS on M1, DLPFC, and placebo stimulation. * Reporting any adverse effects of the intervention. Adult participants with fibromyalgia will be randomized into three groups: a) anodal tDCS over M1 + telerehabilitation, b) anodal tDCS over DLPFC + telerehabilitation, and c) sham-tDCS + telerehabilitation. The intervention will last for 12 weeks. The telerehabilitation exercise program will include an aerobic phase and a resistance phase, with four intensity levels regulated based on the Borg Rating of Perceived Exertion (0-10). The program will be conducted remotely through phone contact, with materials and videos provided to guide exercise execution. tDCS will be applied once per week for 20 minutes at 2 mA, either over M1 or DLPFC. The dependent variables-pain intensity, fibromyalgia impact, fatigue, anxiety and depression levels, pain catastrophizing, sleep quality, functional capacity, and isometric muscle strength-will be collected in the week prior to the intervention, the week following the intervention, and 12 weeks after its completion. Additionally, pain intensity, fibromyalgia impact, fatigue severity, anxiety and depression levels, pain catastrophizing, and sleep quality will be evaluated during the 6th week of the intervention. Exercise intensity, exercise adherence, and any adverse effects related to the intervention will be recorded weekly.

Effect of Neuromodulation on Pain Biomarkers and Functional Outcome in Patients With Fibromyalgia Syndrome

Fibromyalgia is the third most common musculoskeletal condition in terms of prevalence, after lumbar pain and osteoarthritis. Its prevalence is around 2-4 % and is more frequent in women than in men; the prevalence is highest in age the range of 40-60 years.