Discovery of Sirolimus Sensitive Biomarkers in Blood

NCT03304678 — Phase 2, Completed, 33 participants, National Heart, Lung, and Blood Institute (NHLBI)

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Registry	NCT03304678
Status	Completed
Phase	Phase 2
Study type	Interventional; na, single group, masking: none, other
Enrollment	33 (Actual)
Sponsor	National Heart, Lung, and Blood Institute (NHLBI) (Nih)
Conditions	Lymphangioleiomyomatosis
Interventions	Sirolimus 2mg (Drug)
Dates	start 2017-12-04, primary completion 2025-03-09, completion 2025-03-14, first posted 2017-10-09, last updated 2026-02-18
Locations	1 site in United States

-Summary

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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+Detailed 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.

+Arms and interventions

Arm	Type	Interventions	Description
Participants diagnosed with Lymphangioleiomyomatosis receiving Sirolimus	Other	Drug: Sirolimus 2mg	Participants diagnosed with Lymphangioleiomyomatosis will be administered Sirolimus 2 mg by mouth daily to be prescribed by treating physician.

Sirolimus 2mg (Drug), also known as Rapamune: 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.

+Outcome measures

Primary outcomes

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

+Eligibility

Sex: Female, ages: 18 Years to 90 Years

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

+Posted results

Participant flow

Milestone	Participants Diagnosed With Lymphangioleiomyomatosis Receiving Sirolimus
Started	33
Completed	24
Not completed	9

Outcome results

Number of Sirolimus-Sensitive Plasma Protein Biomarkers in Lymphangioleiomyomatosis (LAM) Participants (Primary), Number, plasma proteins: Participant With LAM Receiving Sirolimus 662

Adverse events

Time frame: Up to 9 months

Arm	Deaths	Serious adverse events	Other adverse events
Participants Diagnosed With Lymphangioleiomyomatosis Receiving Sirolimus	0/32 (0.0%)	0/32 (0.0%)	1/32 (3.1%)

Other adverse events by term

Term	Organ system	Participants Diagnosed With Lymphangioleiomyomatosis Receiving Sirolimus
Pneumothorax	Respiratory, thoracic and mediastinal disorders	1/32

+Locations (1)

Facility	City	Country	Status
National Institutes of Health Clinical Center	Bethesda, Maryland	United States

+Study documents

Study Protocol and Statistical Analysis Plan (PDF, 2021-11-01)

+Investigators

Joel Moss, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)

My Notes

Public

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