Impact of Major Ozone Autohemotherapy on Sarcopenia Parameters in Fibromyalgia

Official title

Effects of Major Ozone Autohemotherapy on Sarcopenia Parameters and Clinical Features in Fibromyalgia

Overview

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

• Other Major Ozone Autohemotherapy
  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.
• Other Placebo 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.
• Other Exercise 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

Primary outcome measures

• Change in Fibromyalgia Impact Questionnaire (FIQ) Total Score [Time frame: Baseline (Day 0) to Month 3]

Secondary outcome measures (12)

• Change in Fatigue Severity Scale (FSS) Score [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Pittsburgh Sleep Quality Index (PSQI) Global Score [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Health-Related Quality of Life (SF-12 PCS) [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Health-Related Quality of Life (SF-12 MCS) [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Pain Intensity (Visual Analog Scale, VAS) [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Anxiety Symptoms (Hospital Anxiety and Depression Scale-Anxiety, HADS-A) [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Depressive Symptoms (Hospital Anxiety and Depression Scale-Depression, HADS-D) [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Morning Fasting Serum Cortisol Level [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Rectus Femoris Muscle Thickness (Ultrasound) [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Rectus Femoris Cross-Sectional Area (Ultrasound) [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Rectus Femoris Pennation Angle (Ultrasound) [Time frame: Baseline (Day 0), Week 6, and Month 3]
• Change in Rectus Femoris Fascicle Length (Ultrasound) [Time frame: Baseline (Day 0), Week 6, and Month 3]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Turkey (Türkiye) · 1 center

• Sakarya Training and Research Hospital — Sakarya

Identifiers

NCT: NCT07680621 · UZUN-FTR-EU-54

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗