Discovery of Sirolimus Sensitive Biomarkers in Blood

Study Overview
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Brief Summary
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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 3 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. Participant samples will be stored in a secure place. No personal data will be connected to them.

Detailed Description
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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.

Official Title
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Discovery of Sirolimus Sensitive Biomarkers in Blood

Conditions
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Lymphangioleiomyomatosis

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA 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 EXCLUSION CRITERIA 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| taking sirolimus<br>Subjects will come to the NIH and begin taking sirolimus 2mg | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to identify if miRNA are responsive to sirolimus in patients with LAM | identify if miRNA are responsive to sirolimus in patients with LAM | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mTORC1 Inhibition, VEGF-D, MicroRNA, Natural History