Therapeutic Value of Sirolimus in Refractory Adult-Onset Still's Disease
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- AOSD Disease Activity Score
研究概览
简要总结
This study aims to further evaluate the anti-inflammatory effects of the mTOR inhibitor sirolimus in patients with adult-onset Still's disease (AOSD), and to verify whether it can reduce inflammation and control disease activity by restoring ZFP36L2 expression and promoting the degradation of inflammatory cytokine mRNAs. A total of three patients with refractory AOSD will be enrolled, defined as those showing no significant improvement after treatment with glucocorticoids at 1 mg/kg, or experiencing relapse during tapering of glucocorticoids to 15 mg/day. On the basis of their existing therapy, patients will receive oral sirolimus at a dose of two capsules per day, one in the morning and one in the evening. On the day prior to initiating sirolimus and at weeks 4, 8, and 12 of treatment, 10 ml of peripheral blood will be collected by trained medical staff, and neutrophils will be isolated within 2 hours to assess ZFP36L2 expression levels. Throughout treatment, patients' clinical manifestations, including fever, rash, and joint pain, will be monitored, and dynamic changes in multiple inflammation-related markers will be measured in peripheral blood at weeks 4, 8, and 12. These include C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum ferritin, soluble interleukin-2 receptor (sIL-2R), and a panel of cytokines. Finally, correlations among sirolimus treatment, ZFP36L2 expression, inflammatory responses, and disease activity will be analyzed to explore its potential therapeutic mechanisms in AOSD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age over 18 years;
- •Meeting the Yamaguchi criteria, with infection and malignancy excluded;
- •Meeting the definition of refractory AOSD, i.e., patients whose symptoms show no significant improvement after treatment with glucocorticoids at 1 mg/kg, or who experience relapse during tapering of glucocorticoids to 15 mg/d;
- •Complete clinical information;
- •Signed and dated informed consent form;
- •Willingness to comply with study procedures and cooperate throughout the entire study.
排除标准
- •Presence of other rheumatic diseases;
- •History of, or planned, hematopoietic stem cell transplantation;
- •Presence of severe comorbidities considered by the investigator to be unsuitable for participation in this clinical study, such as severe cardiac or pulmonary insufficiency, severe bone marrow suppression, or severe hepatic or renal dysfunction;
- •Acute conditions such as bowel perforation or complete intestinal obstruction;
- •Pregnant, planning pregnancy, or breastfeeding women;
- •Poor compliance.
研究组 & 干预措施
Sirolimus combination therapy group
On the basis of the existing treatment, oral sirolimus will be added at a dose of two capsules per day, one in the morning and one in the evening.
干预措施: add-on sirolimus therapy (Drug)
结局指标
主要结局
AOSD Disease Activity Score
时间窗: at weeks 12
Pouchot Systemic Score Scoring items (1 point each): fever; arthritis/arthralgia; rash; sore throat; hepatosplenomegaly; pericarditis/pleuritis; lymphadenopathy; abnormal liver function; leukocytosis; hyperamylasemia/thrombocytopenia; elevated ESR or CRP; other systemic manifestations (e.g., myalgia, fatigue). Total score: 0-12 points, with higher scores indicating greater disease activity.
次要结局
- AOSD Disease Activity Score(Baseline (day before sirolimus) and at weeks 4, and 8)
- Serum C-reactive Protein (CRP) Concentration(Baseline (day before sirolimus) and at weeks 4, 8, and 12)
- Erythrocyte Sedimentation Rate (ESR)(Baseline (day before sirolimus) and at weeks 4, 8, and 12)
- Concentration of Serum Ferritin(Baseline (day before sirolimus) and at weeks 4, 8, and 12)
- Level of Soluble Interleukin-2 Receptor (sIL-2R)(Baseline (day before sirolimus) and at weeks 4, 8, and 12)
- Concentration of Inflammatory Cytokines (e.g., IL-6, TNF-α)(Baseline (day before sirolimus) and at weeks 4, 8, and 12)
- Number of participants with Clinical symptoms such as rash and arthralgia(Baseline (day before sirolimus) and at weeks 4, 8, and 12)
- Expression level of ZFP36L2 in neutrophils(Baseline (day before sirolimus) and at weeks 4, 8, and 12)