LymphangioleiomyomatosisPhase 2NCT03304678
Discovery of Sirolimus Sensitive Biomarkers in Blood
A Phase 2 study testing Sirolimus 2mg in people with Lymphangioleiomyomatosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years, women only
- Conditions the study is for
- Lymphangioleiomyomatosis
- What is being tested?
- Sirolimus 2mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Dec 2017to 14 Mar 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Lymphangioleiomyomatosis
- Being tested
- Sirolimus 2mg
- Keywords
- mTORC1 Inhibition, VEGF-D, MicroRNA, Natural History
- Medical subject headings
- Lymphangioleiomyomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sirolimus 2mgDrug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Sirolimus 2mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2017
- Study start4 Dec 2017
- Primary completion9 Mar 2025
- Study completion14 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LymphangioleiomyomatosisStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joel Moss, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03304678
- Sponsor's protocol ID
- 180003
- Other IDs
- 18-H-0003
- Status last verified
- 3 Feb 2026
- First submitted
- 6 Oct 2017
- Last updated
- 18 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication.
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Discovery of Sirolimus Sensitive Biomarkers in Blood
- ClinicalTrials.gov ID
- NCT03304678
- Acronym / sponsor ID
- 180003
- Conditions
- Lymphangioleiomyomatosis
- Keywords
- mTORC1 Inhibition, VEGF-D, MicroRNA, Natural History
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 4 Dec 2017 (actual)
- Primary completion
- 9 Mar 2025 (actual)
- Study completion
- 14 Mar 2025 (actual)
- First posted
- 9 Oct 2017 (actual)
- Results
- Posted 18 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants diagnosed with Lymphangioleiomyomatosis receiving Sirolimus | Other | Drug: Sirolimus 2mgParticipants diagnosed with Lymphangioleiomyomatosis will be administered Sirolimus 2 mg by mouth daily to be prescribed by treating physician. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sirolimus 2mgAlso: RapamunePatients 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. | Drug | Participants diagnosed with Lymphangioleiomyomatosis receiving Sirolimus |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joel Moss, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sirolimus 2mg in people with Lymphangioleiomyomatosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2026.