Fibromyalgia
Conditions
Brief summary
Fibromyalgia syndrome (FMS) is a chronic and heterogeneous disorder characterized primarily by widespread pain, accompanied by sleep disturbances, fatigue, depressive symptoms, and cognitive dysfunction. Although multiple therapeutic options are available, no curative treatment currently exists. Previous studies have demonstrated increased oxidative stress, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and a predisposition to sarcopenia in patients with FMS. Ozone therapy has increasingly been used in chronic diseases due to its regulatory effects on oxidative stress. Although ozone is inherently an oxidative molecule, when administered at therapeutic doses it may induce antioxidant responses at the cellular level and exert anti-inflammatory effects by modulating inflammatory mediators. However, limited studies have evaluated the efficacy and underlying mechanisms of major ozone autohemotherapy (MOA) in FMS. This controlled, prospective, single-blind study aims to investigate the effects of major ozone autohemotherapy on clinical parameters of FMS, as well as its impact on HPA axis function and sarcopenia-related parameters. A total of 60 patients with FMS will be enrolled and randomized into two groups: (1) exercise therapy alone and (2) exercise therapy plus major ozone autohemotherapy. MOA will be administered twice weekly for a total of 10 sessions at a dose of 20-40 μg/mL. Participants will be evaluated at baseline, at week 6, and at 3 months. Outcome measures will include Visual Analog Scale (VAS), Fibromyalgia Impact Questionnaire (FIQ), Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index (PSQI), Short Form-12 (SF-12), and Hospital Anxiety and Depression Scale (HADS). Morning fasting serum cortisol levels will be measured to assess HPA axis function. Sarcopenia assessment will include handgrip strength measured by Jamar dynamometer, and ultrasonographic evaluation of muscle mass, muscle thickness, pennation angle, fascicle length, echogenicity, and cross-sectional area. Physical performance will be assessed using the Short Physical Performance Battery (SPPB). Unlike previous studies, this trial includes a 3-month follow-up evaluation after completion of ozone therapy to assess longer-term effects. By incorporating objective sarcopenia and endocrine assessments alongside validated clinical scales, the study aims to provide comprehensive evidence regarding the role of major ozone autohemotherapy in FMS management. This will be the first study to specifically evaluate the effects of major ozone autohemotherapy on sarcopenia parameters in patients with FMS.
Interventions
Major ozone autohemotherapy will be administered twice weekly for a total of 10 sessions. In each session, 100 mL of venous blood will be withdrawn into a sterile citrate-containing glass bottle, mixed with 100 mL of an ozone-oxygen gas mixture at a concentration of 20-40 μg/mL, and reinfused intravenously over approximately 7-10 minutes. The procedure will be performed by certified physicians according to the Madrid Declaration on Ozone Therapy guidelines.
OTHERPlacebo Ozone Autohemotherapy
The placebo procedure will be identical to the active major ozone autohemotherapy protocol; however, a non-therapeutic ozone concentration (0.1 μg/mL) will be used. Blood withdrawal, mixing, and reinfusion procedures will be performed in the same manner to maintain blinding.
OTHERExercise Therapy
Participants will undergo a supervised exercise program twice weekly for 3 months. Each 60-minute session will include warm-up walking, aerobic exercise at 60-65% of maximum heart rate, strengthening exercises targeting major muscle groups, and stretching exercises. Exercise intensity will be gradually progressed if tolerated without symptom exacerbation
Sponsors
Sakarya University
The Scientific and Technological Research Council of Turkey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Female patients aged 18-65 years * Diagnosis of fibromyalgia syndrome according to the 2016 ACR criteria: * Symptoms present at a similar level for at least 3 months * Widespread Pain Index (WPI) ≥ 7 and Symptom Severity Scale (SSS) ≥ 5 * WPI 4-6 and SSS ≥ 9 * Not currently receiving medical treatment for fibromyalgia (except NSAIDs)
Exclusion criteria
* Current or previous pharmacological treatment specifically for fibromyalgia * Pregnancy or breastfeeding * History of active or previous malignancy * History of systemic inflammatory diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, dermatomyositis, familial Mediterranean fever) * Endocrine disorders (e.g., hypothyroidism, Cushing's syndrome, adrenal insufficiency) * Anemia * Chronic renal failure * Chronic liver failure * Chronic obstructive pulmonary disease (COPD) * Known severe cardiovascular disease * Body mass index (BMI) \> 30 kg/m² * Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fibromyalgia Impact Questionnaire (FIQ) Total Score | Baseline (Day 0) to Month 3 | The Fibromyalgia Impact Questionnaire (FIQ) will be used to assess overall disease impact and functional status. The total score ranges from 0 to 100, with higher scores indicating greater disease impact/severity. The primary endpoint is the between-group difference in change in FIQ total score from baseline to Month 3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fatigue Severity Scale (FSS) Score | Baseline (Day 0), Week 6, and Month 3 | Fatigue will be assessed using the Fatigue Severity Scale (FSS). The score is calculated as the mean of 9 items rated 1-7; higher scores indicate more severe fatigue. |
| Change in Pittsburgh Sleep Quality Index (PSQI) Global Score | Baseline (Day 0), Week 6, and Month 3 | Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI) global score (range 0-21). Higher scores indicate worse sleep quality; scores \>5 suggest poor sleep quality. |
| Change in Health-Related Quality of Life (SF-12 PCS) | Baseline (Day 0), Week 6, and Month 3 | Health-related quality of life will be assessed using the Short Form-12 (SF-12), generating Physical Component Summary (PCS) scores. Higher scores indicate better health status |
| Change in Health-Related Quality of Life (SF-12 MCS) | Baseline (Day 0), Week 6, and Month 3 | Health-related quality of life will be assessed using the Short Form-12 (SF-12), generating Mental Component Summary (MCS) scores. Higher scores indicate better health status |
| Change in Pain Intensity (Visual Analog Scale, VAS) | Baseline (Day 0), Week 6, and Month 3 | Pain intensity will be assessed using a 10-cm Visual Analog Scale (VAS), where 0 indicates "no pain" and 10 indicates "worst imaginable pain." |
| Change in Anxiety Symptoms (Hospital Anxiety and Depression Scale-Anxiety, HADS-A) | Baseline (Day 0), Week 6, and Month 3 | Anxiety symptoms will be assessed using the HADS-Anxiety subscale (HADS-A), scored 0-21; higher scores indicate greater anxiety severity |
| Change in Depressive Symptoms (Hospital Anxiety and Depression Scale-Depression, HADS-D) | Baseline (Day 0), Week 6, and Month 3 | Depressive symptoms will be assessed using the HADS-Depression subscale (HADS-D), scored 0-21; higher scores indicate greater depressive symptom severity |
| Change in Morning Fasting Serum Cortisol Level | Baseline (Day 0), Week 6, and Month 3 | Morning fasting venous blood samples will be collected between 08:00 and 09:00 to measure serum cortisol as an indicator of hypothalamic-pituitary-adrenal (HPA) axis activity |
| Change in Rectus Femoris Muscle Thickness (Ultrasound) | Baseline (Day 0), Week 6, and Month 3 | Rectus femoris muscle thickness will be measured by ultrasound at a standardized midpoint between the greater trochanter and the superior pole of the patella. The mean of three measurements will be recorded. |
| Change in Rectus Femoris Cross-Sectional Area (Ultrasound) | Baseline (Day 0), Week 6, and Month 3 | Rectus femoris cross-sectional area will be measured by ultrasound by tracing the muscle borders at the standardized measurement site |
| Change in Rectus Femoris Pennation Angle (Ultrasound) | Baseline (Day 0), Week 6, and Month 3 | Pennation angle will be measured on longitudinal ultrasound images as the angle between muscle fascicles and the deep aponeurosis of the rectus femoris. |
| Change in Rectus Femoris Fascicle Length (Ultrasound) | Baseline (Day 0), Week 6, and Month 3 | Fascicle length will be measured on longitudinal ultrasound images. When the entire fascicle is not visible, estimated fascicle length will be derived using muscle thickness and pennation angle. |
| Change in Rectus Femoris Echogenicity (Ultrasound Image Analysis) | Baseline (Day 0), Week 6, and Month 3 | Muscle echogenicity will be quantified from rectus femoris ultrasound images using 8-bit grayscale analysis (0-255) as an indicator of muscle quality and fatty infiltration. |
| Adverse Events | Throughout the study period (up to Month 3) | All adverse events occurring during the intervention period will be recorded and summarized by study group. |
Countries
Turkey (Türkiye)
Contacts
CONTACTEmre Uzun, MD
Outcome results
None listed