Discovery of Sirolimus Sensitive Biomarkers in Blood

National Institutes of Health (NIH)

Status and phase: Completed; Phase 2

Conditions: Lymphangioleiomyomatosis

Treatments: Drug: Sirolimus 2mg

Study type: Interventional

Funder types: NIH

Identifiers

NCT03304678

18-H-0003

180003

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 33 patients

Sex: Female

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• 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

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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33 participants in 1 patient group

Treatment with sirolimus

Other group

Description:

Lymphangioleiomyomatosis (LAM) is a cystic lung disease characterized by proliferation of cells with mutations in the tuberous sclerosis complex (TSC) which leads to activation of the mTORC pathway.

Treatment:

Drug: Sirolimus 2mg