Completed

NCT Number: NCT03304678

Discovery of Sirolimus Sensitive Biomarkers in Blood

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.

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Key information

Conditions

Lymphangioleiomyomatosis Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphangiomyoma Lymphatic Diseases Lymphoproliferative Disorders Neoplasm, Lymphatic Tissue Neoplasms Neoplasms by Histologic Type Neoplasms, Connective and Soft Tissue Perivascular Epithelioid Cell Neoplasms

Age range

18 year–90 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sirolimus 2mg

Drug

Patients with LAM, whose treating physicians have decided that they need to start treatment with sirolimus will be referred to the NIH Clinical Center for these studies.

Other names: Rapamune

Primary outcomes

Number of Sirolimus-Sensitive Plasma Protein Biomarkers in Lymphangioleiomyomatosis (LAM) Participants

Time frame: 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.

Sponsors and collaborators

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Nih

Registry information

Important dates

Study start: 2017
Primary completion: 2025
Study completion: 2025
First posted: Oct 9, 2017
Registry last updated: Feb 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed