Dipyridamole Assessment for Flare Reduction in SLE
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
研究概览
简要总结
Dipyridamole, a medication extensively used in combination with aspirin for stroke prevention, is a promising new treatment for lupus. Dipyridamole has been shown to inhibit certain lymphocyte populations that are over-reactive in lupus and to delay the emergence of lupus-related pathology in mice with lupus. The investigators are interested in investigating the efficacy of dipyridamole in preventing flares in patients with lupus and its impact on biomarkers of disease activity.
详细描述
T cells in systemic lupus erythematosus (SLE) express an abnormal phenotype characterized by increased effector functions and deficient regulatory responses. Dipyridamole, a phosphodiesterase inhibitor extensively used in combination with low dose aspirin in secondary stroke prevention, has been proposed as a specific T cell directed treatment for SLE. Dipyridamole inhibits the calcium/calcineurin/NF-AT pathway in SLE T cells in vitro and abrogates expression of cytokines and costimulatory molecules, eventually also affecting B cell responses. Dipyridamole delays the emergence of lupus related pathology in lupus prone mice, but has not yet been studied in humans with SLE. The investigators aim to investigate the efficacy of dipyridamole in the prevention of flares in SLE patients after withdrawal of background immunosuppressive medications. The investigators will additionally evaluate the safety and tolerability of dipyridamole and its impact on quality of life measures in this population. Furthermore, the effect of dipyridamole on T and B cell biomarkers will be examined.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with SLE meeting the 1997 ACR Classification Criteria
- •Evidence of positive ANA or anti-dsDNA within one year of screening
- •SLEDAI ≥4 or ≥1 BILAG A or B at screening, despite standard of care
排除标准
- •Leukopenia (WBC <2.000/mm3) or lymphopenia (lymphocytes < 300/mm3)
- •AST or ALT >3 times above normal cut off values
- •Acute lupus nephritis defined as class II, IV or V nephritis diagnosed within 6 months or prot/creat > 1.5 gm/gm due to active lupus or in process of receiving induction therapy for nephritis
- •Active CNS lupus affecting mental status
- •Pregnancy or breast feeding
- •Current requirement for anticoagulation
- •Contraindication to aspirin or dipyridamole, including history of recent or severe GI bleeding, hemoglobin <9 mg/dL, platelet count of <30,000 /mm3 or unstable platelet count
- •Any other medical condition, whether or not related to lupus which, in the opinion of the investigator would render the patient inappropriate or too unstable to complete the study protocol
- •Inability or unwillingness to understand and/or sign informed consent
研究组 & 干预措施
extended release dipyridamole/aspirin
extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks
干预措施: extended release dipyridamole 200mg/aspirin 25mg (Drug)
aspirin
half a tablet of a 81mg aspirin twice daily for 24 weeks
干预措施: 81mg aspirin (Drug)
结局指标
主要结局
British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
时间窗: 24 weeks
This is a landmark measure of percentage of patients who meet response criteria. To meet the BICLA response measure a patient must, compared to baseline, have a decrease in all moderate or severe scores on the British Isles Lupus Assessment Group (BILAG) index by at least one severity grade (Severe disease (BILAG A score) must drop to at least moderate (B or better) and B must drop to at least mild (C or not present). Also, there must be no increase in any other BILAG organ scores, no increase in The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and no increase in the physician's global assessment (PGA) by more than 10% of the scale. Furthermore, there may no off protocol medication increases. Note on all scales mentioned a higher score signifies greater disease activity. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76.
次要结局
- Systemic Lupus Erythematosus Responder Index (SRI) 4(24 weeks)
- SRI Component Analyses: 4 Point Drop in SLEDAI(24 weeks)