Clinical trial NCT06653686: Study on the Efficacy and Safety of Thermotherapy in the Treatment of Refractory Gout
Official title: Study on the Efficacy and Safety of Extracorporeal High-Frequency Hyperthermia in the Treatment of Refractory Gout
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Refractory Gout
Lead sponsor: The First Hospital of Jilin University
Sponsor class: OTHER
First posted: 2024-10-22
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Gout is a crystal-related arthropathy caused by purine metabolism disorder or decreased uric acid excretion. It can manifest as acute recurrent arthritis, tophus formation, tophaceous chronic arthritis, and urate nephropathy, with severe cases potentially leading to joint disability, renal insufficiency, and damage to other vital organs.Poor long-term control of uric acid levels may result in the progression of refractory gout in some patients, characterized by persistently elevated serum uric acid levels, recurrent acute arthritis, and multiple or progressive tophi, severely affecting quality of life and imposing a significant economic burden on patients.Currently, clinical research on refractory gout is relatively limited, and both domestic and international guidelines continue to recommend uric acid-lowering therapy to slow disease progression.However, due to poor adherence, intolerance to uric acid-lowering drugs, or dose limitations caused by coexisting chronic kidney disease, achieving target serum uric acid levels in these patients is often difficult, and their clinical symptoms are challenging to alleviate effectively.

In recent years, thermotherapy, as a non-pharmacological treatment modality, has garnered increasing attention for its effects in alleviating chronic pain, promoting blood circulation, and reducing inflammatory responses.Its primary mechanisms include: 1) increasing local temperature to influence the solubility of monosodium urate (MSU) crystals, promoting their dissolution, reducing gout attacks, and accelerating the resolution of gout flares;2) elevated local temperature promotes vasodilation and blood circulation, increasing the supply of oxygen and nutrients, facilitating the clearance of uric acid and inflammatory mediators;3) thermotherapy enhances local immune responses by boosting cellular phagocytic activity; 4) it may act as a stimulus transmitted to the central nervous system alongside pain impulses, disrupting pain transmission pathways and resulting in the attenuation or elimination of pain sensations. In recent years, thermotherapy has been widely used in clinical practice as a non-invasive, adjunctive treatment for various conditions, such as tumors, lumbar disc herniation, chronic prostatitis, pelvic inflammatory disease, endometriosis-associated dysmenorrhea, and osteoarthritis, due to its proven efficacy, non-invasive nature, and minimal adverse effects.A study from China demonstrated that thermotherapy has significant therapeutic effects on patients with acute gout attacks, effectively alleviating acute symptoms and reducing inflammatory responses. In this study, the overall clinical efficacy rate of the treatment group (thermotherapy combined with conventional therapy) was significantly higher at 90.0% compared to 72.5% in the control group. Moreover, on day 1 and day 3 post-treatment, the VAS scores of the treatment group (4.11±0.76, 3.23±0.53) were significantly lower than those of the control group (5.23±1.21, 4.23±0.76), and the treatment group had lower ESR and CRP levels than the control group after treatment (P\<0.05).Therefore, the primary aim of this study is to investigate the efficacy of thermotherapy in reducing gout attacks. However, there is currently no large-scale, multicenter clinical research evidence evaluating the clinical effectiveness of thermotherapy in patients with refractory gout.

In summary, considering the critical regulatory role of temperature in the formation and deposition of monosodium urate crystals and the fundamental principles of extracorporeal high-frequency thermotherapy, we hypothesize that extracorporeal high-frequency thermotherapy could reasonably reduce MSU crystal burden, lower uric acid levels, alleviate local inflammation, and decrease the frequency of gout attacks through its thermal effects.This study aims to evaluate the efficacy of extracorporeal high-frequency thermotherapy in patients with refractory gout through a randomized controlled trial, exploring its effects on reducing gout attack frequency, improving uric acid metabolism, and alleviating inflammation. Additionally, the study will assess the impact of thermotherapy on patients' quality of life, physical function, and metabolic parameters, with the goal of providing new effective strategies for the treatment of refractory gout in the future.


Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 80 years old;
2. Meeting the diagnostic criteria for refractory gout, defined as fulfilling at least one of the following three conditions: 1) Blood uric acid remains ≥360 μmol/L despite adequate doses and duration of urate-lowering drugs, either alone or in combination (adequate treatment is defined as single-drug therapy at standard doses for more than 6 months, or maximum doses for more than 3 months, with blood uric acid still ≥360 μmol/L; combination therapy for more than 3 months with blood uric acid still ≥360 μmol/L); 2) More than two gout flares per year despite standardized treatment; 3) Presence of multiple or progressive tophi;
3. History of at least three gouty arthritis flares in the past 12 months prior to enrollment;
4. Understanding the purpose and procedures of the study and providing signed informed consent.

Exclusion Criteria:

1. Acute gout flare within 2 weeks prior to screening;
2. Secondary gout due to hematological diseases, chemotherapy, radiotherapy, renal failure, or medications (e.g., diuretics such as furosemide, torsemide, hydrochlorothiazide, aspirin, niacin \[vitamin B3\], antituberculosis drugs, immunosuppressants such as cyclosporine);
3. Other secondary joint pain (e.g., joint pain caused by rheumatoid arthritis or systemic lupus erythematosus) or joint pain of unknown cause;
4. Patients with cardiac, pulmonary, hepatic, or renal insufficiency; active tuberculosis; mental illness or consciousness disorders;
5. Patients with bone marrow hematopoietic insufficiency; leukemia; a tendency for major bleeding; or a history of malignant tumors;
6. Polyarticular gouty arthritis involving more than four joints;
7. Presence or suspicion of active or recurrent bacterial, fungal, or viral infections, including tuberculosis, HIV, or hepatitis B or C infections;
8. Allergy to the study drugs; patients with heat insensitivity;
9. Patients currently using mercaptopurine or azathioprine; patients taking CYP3A4 inhibitors or P-gp inhibitors;
10. Major surgery within the last 3 months or unhealed surgical wounds;
11. Presence of stents or metal implants;
12. Local skin lesions or infections;
13. Pregnant or breastfeeding women.

Primary outcomes:
measure: The number of gout flares during the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
Secondary outcomes:
measure: The proportion of patients experiencing ≥1 or ≥2 gout flares during the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: The time to the first gout flare during the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Changes in serum uric acid levels by the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Proportion of patients achieving target uric acid levels by the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Percentage reduction in febuxostat dosage by the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Changes in the volume of monosodium urate (MSU) in target joints by the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Changes in C-reactive protein (CRP) levels by the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Changes in erythrocyte sedimentation rate (ESR) by the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Changes in TH1/TH2-related cytokines by the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Changes in fasting blood glucose at the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Changes in lipid levels at the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Changes in quality of life by the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Changes in physical function by the end of the treatment period
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Comparison of patient treatment satisfaction at the end of the treatment period.
timeFrame: From enrollment to the end of treatment at 20 weeks
measure: Incidence of adverse events
timeFrame: From enrollment to the end of study at 24 weeks
Other outcomes:
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