Discovery of Sirolimus Sensitive Biomarkers in Blood
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Number of Sirolimus-Sensitive Plasma Protein Biomarkers in Lymphangioleiomyomatosis (LAM) Participants
研究概览
简要总结
Background:
Lymphangioleiomyomatosis (LAM) is a rare, progressive disease. It usually affects women in the prime of their lives. It typically results in lung destruction. Studies have shown that a drug called sirolimus stabilizes lung function in people with LAM. But researchers do not know what drug dose and blood serum levels are needed to reach this stability. Researchers want to learn more about the right dose of sirolimus for people with LAM.
Objective:
To determine if blood and urine markers after 1 dose and again after 9 months can be used to evaluate the correct dose of sirolimus for people with LAM.
Eligibility:
Women ages 18-90 with LAM whose doctors have decided they should start taking sirolimus to treat it.
Design:
At visit 1, participants will take their first dose of sirolimus by mouth at the clinic. They will have blood and urine collected.
Participants will take 1 tablet of the study drug each day.
Visit 2 will be 3 months after visit 1. Participants will have blood and urine collected.
Visit 3 will be 9 months after visit 1. Participants will have blood and urine collected.
Participant samples will be stored in a secure place. No personal data will be connected to them.
详细描述
Sirolimus (rapamycin), which acts as a targeted inhibitor of the protein mechanistic target of rapamycin (mTOR), has been shown to be effective in patients with lymphangioleiomyomatosis (LAM). It stabilizes lung function, resolves chylous effusions and lymphangioleiomas and shrinks angiomyolipomas. The current study is to understand better the short-term action of the drug by following the effects on potential biomarkers in blood and urine. Patients with LAM will have samples taken prior to administration of first dose of the drug, at 1 hr and then at 23 hours after the drug (trough level). At 3 and 9 months, samples will be obtained at trough and 1 hour after the dose. Molecular and cellular analyses will be performed to look for potential biomarkers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female 18 to 90 years of age
- •Diagnosis of LAM
- •Initiation of sirolimus therapy (2mg daily) based on standard-of-care pulmonary indications and the advice of the patient s local physician
排除标准
- •Unable to travel to the NIH
- •Unable to provide informed consent
- •Advanced stage of a pulmonary or a systemic illness in which the risk of the study is judged to be significant even in the absence of a clear contraindication to the procedures
- •Women who are pregnant or lactating
研究组 & 干预措施
Participants diagnosed with Lymphangioleiomyomatosis receiving Sirolimus
Participants diagnosed with Lymphangioleiomyomatosis will be administered Sirolimus 2 mg by mouth daily to be prescribed by treating physician.
干预措施: Sirolimus 2mg (Drug)
结局指标
主要结局
Number of Sirolimus-Sensitive Plasma Protein Biomarkers in Lymphangioleiomyomatosis (LAM) Participants
时间窗: Day 0 (pre-treatment, 1 hour post-Sirolimus, 23 hours post-Sirolimus), Month 3 (23 hours post-Sirolimus, 1 hour post next dose), Month 9 (23 hours post-Sirolimus, 1 hour post next dose)
Plasma from Lymphangioleiomyomatosis (LAM) participants was profiled using the aptamer-based Somascan 11k assay (Somalogic). The primary outcome is the number of plasma proteins that exhibit a statistically significant change from each participant's baseline following sirolimus administration, defined by pre-specified multiplicity-adjusted thresholds (e.g., FDR q\<0.05 with absolute log2 fold-change ≥0.5), representing candidate sirolimus-sensitive biomarkers.
次要结局
未报告次要终点