Discovery of Sirolimus Sensitive Biomarkers in Blood

NCT03304678 | Completed Phase 2 Results

• 2 other identifiers: 18000318-H-0003
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Lymphangioleiomyomatosis

Keywords

mTORC1 Inhibition; VEGF-D; MicroRNA; Natural History

Outcome Measures

Primary Outcomes (1)

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

  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.

  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)

Study Arms (1)

Participants diagnosed with Lymphangioleiomyomatosis receiving Sirolimus

OTHER

Participants diagnosed with Lymphangioleiomyomatosis will be administered Sirolimus 2 mg by mouth daily to be prescribed by treating physician.

Drug: Sirolimus 2mg

Interventions

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.

Also known as: Rapamune

Participants diagnosed with Lymphangioleiomyomatosis receiving Sirolimus

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphangioleiomyomatosis

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Joel Moss, M.D., Ph.D.
• Organization: National Heart, Lung, and Blood Institute (NHLBI)

mossj@nhlbi.nih.gov

301.496.1597

Study Officials

• Joel Moss, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: October 9, 2017
• Study Start: December 4, 2017
• Primary Completion: March 9, 2025
• Study Completion: March 14, 2025
• Last Updated: February 18, 2026
• Results First Posted: February 18, 2026

Record last verified: 2026-02-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available as soon as possible or at the time of associated publication, whichever comes first, according to Institute policy.
• Access Criteria: BioData Catalyst is supported by NHLBI and access to data is controlled by the NHLBI Data Access Committee (DAC) utilizing the database (dbGaP)

Locations

US (1)