Prospective Study of Rapamycin for the Treatment of SLE
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 99
- 试验地点
- 1
- 主要终点
- Reduction of the Disease Activity as Measured by SLEDAI and BILAG Scores.
研究概览
简要总结
Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin. It involves multiple organs including the joints, skin, kidneys and central nervous system. The disease process is caused by a dysfunction of the immune system. The drugs currently used for the treatment of SLE are only partially effective and carry significant risks for side-effects. Patients that were resistant or intolerant to conventional medication have been effectively treated with Rapamycin and were able to decrease the amount of prednisone they needed.
The purpose of this study is to prospectively determine the therapeutic efficacy and mechanism of action of Rapamune in patients with SLE. Healthy subjects not receiving Rapamune will be asked to donate blood to serve as controls only for immunobiological outcomes.
As part of the research effort to understand the reason for the variations in the effects of treatment drugs by different individuals, a sub-study of the DNA makeup of subjects enrolled in the trial will also be done. The purpose of the sub-study is to possibly determine whether different responses to the drugs used to treat SLE have a correlation with the differences in the genetic makeup of the subjects.
详细描述
43 SLE subjects and 56 healthy controls are being recruited. The study will last 1 year with 9 study visits from day 0 to day 360. The healthy controls only need to donate blood once.
The study drug, sirolimus, is taken by mouth at a starting dose of 2mg/day. The dose is adjusted to achieve blood levels in the range of 6-15 ng/ml (the levels found to be effective for preventing organ rejections).
Blood samples are obtained before taking sirolimus, every two weeks for the first month, then every three months until 1 year, and then three months later to check the effect of discontinuing rapamycin. Each SLE subject will be asked to provide up to 100 ml (20 teaspoons) of blood at each visit. The first 6 visits will take place within 3 months and the remaining 3 visits every 3 months.
Routine laboratory work will be performed. Part of the blood drawn will be used for research and part will be used for routine lab work as part of standard of care.
The non-routine laboratory studies include:
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
- 是
入选标准
- •For SLE Subjects:
- •SLE patients who exhibit ongoing disease activity by SLEDAI greater or equal to
- •SLE patients whose disease activity is controlled by administration of corticosteroids, most commonly, at least 10 mg/day of prednisone.
- •18 years of age or older.
- •Updated vaccinations prior to study entry.
- •Use of effective contraception for male patients before, during and up to 12 weeks after sirolimus therapy.
- •For Healthy Control Subjects:
- •18 years of age or older
- •Must be matched with one of the SLE patients enrolled in the study by age, gender and ethnic origin
- •Must not have any acute or chronic illness.
排除标准
- •For SLE Subjects:
- •Patients who are pregnant.
- •Patients with allergy or intolerance to sirolimus.
- •Patients with life-threatening manifestations of SLE.
- •Patients with proteinuria exceeding 500 mg/24 h or urine protein/creatine ratio >0.
- •Patients with total cholesterol > 300 mg/dl or triglyceride > 400 mg.dl will be excluded.
- •Patients with acute infection requiring antibiotics.
- •Patients on sirolimus who develop infections and require intravenous antibiotics and fail to show clinical improvement in 5 days.
- •Patients concurrently undergoing B cell-depleting therapy, cyclophosphamide, cyclosporine, and tacrolimus.
- •Patients who have received investigational biologic B-cell depleting products within one year of study initiation.
- •Patients with a history of chronic viral infections (e.g., HIV, hepatitis B, hepatitis C) or with a history of a malignancy (except non-melanoma skin cancer).
- •Due to interference with sirolimus metabolism, subjects will not be allowed to receive concomitant rifampin, ketoconazole,voriconazole, itraconazole, erythromycin, or clarithromycin during the study.
- •Patients with any type of interstitial lung disease.
- •For Healthy control Subjects:
- •Subjects who are pregnant.
- •Subjects with any acute or chronic illness.
研究组 & 干预措施
SLE subjects
SLE subjects receiving the study drug, Rapamune.
干预措施: Rapamycin (Drug)
结局指标
主要结局
Reduction of the Disease Activity as Measured by SLEDAI and BILAG Scores.
时间窗: 1 year
The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and The British Isles Lupus Assessment Group (BILAG) are clinical tools for assessing disease activity in lupus erythematosus patients. These indices play a central role as core determinants in SLE Responder Index. SLEDAI, comprising 24 items, quantifies disease activity on a scale of 0 to 105. Higher scores indicate more severe disease activity, reflecting cumulative impact of clinical and laboratory variables. BILAG, a comprehensive assessment, encompasses 97 items organized into 9 organ domains. The scoring ranges from A to E: A: No activity B: Mild activity C: Moderate activity D: Severe activity E: Very severe activity Total BILAG score is sum of individual item scores across all domains, with a potential range from 0 (if all items are graded as A, denoting no activity) to 97 (if all items are graded as E, signifying very severe activity). A lower total BILAG score indicates less severe disease activity.
次要结局
- Decrease of the Amount of Prednisone Needed to Control Disease Activity in SLE Patients.(1 year)
研究者
Andras Perl
Professor of Medicine, Division Chief of Rheumatology
State University of New York - Upstate Medical University