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.

Study Overview

• Status: Recruiting
• Conditions: Lymphangioleiomyomatosis
• Intervention / Treatment: Drug: Sirolimus 2mg

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.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tatyana Worthy, R.N.; Phone Number: (301) 827-1376; Email: worthyt@mail.nih.gov
• Study Contact Backup: Name: Joel Moss, M.D.; Phone Number: (301) 496-1597; Email: mossj@nhlbi.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY8664111010 800-411-1222; Email: prpl@cc.nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

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.@@@

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Treatment with sirolimus; 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.	Drug: Sirolimus 2mg; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Joel Moss, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2017
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: October 6, 2017
• First Posted (Actual): October 9, 2017

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 23, 2024
• Last Verified: March 22, 2024

More Information

Terms related to this study

• Keywords: Natural History; MicroRNA; VEGF-D; mTORC1 Inhibition
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphangiomyoma; Lymphatic Vessel Tumors; Perivascular Epithelioid Cell Neoplasms; Lymphangioleiomyomatosis; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 180003; 18-H-0003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No