LAMPhase 3MILEDNCT03150914
Multicenter Interventional Lymphangioleiomyomatosis (LAM) Early Disease Trial
A Phase 3 study testing Sirolimus in people with LAM and Lymphangioleiomyomatosis, run by University of Cincinnati at 8 sites in United States.
Trial summary
This is a study to determine if early, long-term low dose sirolimus is effective for preventing progression to more advanced stages. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- LAM, Lymphangioleiomyomatosis
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 8 sitesUnited States
- Study dates
- 1 Jan 2018to 30 Jun 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female, age 18 or over
- Signed and dated informed consent
- Diagnosis of LAM as determined by compatible lung CT and one of the following
- biopsy (lung, abdominal mass, lymph node or kidney) or cytology from thoracic or abdominal sources revealing LAM, or
- tuberous sclerosis, angiomyolipomata (diagnosed by CT, MRI by the site radiologist or biopsy) or chylous pleural effusion (verified by tap), or
- VEGF-D level ≥ 800 pg/ml.
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- Post-bronchodilator forced expiratory volume in one second of > 70%
- Presence of markers of non-trivial burden of LAM or likely progression based on one of the following:
- pretrial FEV 1 rate of decline of >60cc/yr, comparing enrollment FEV1 to any prior measurement in the past 3 years, or
- baseline supplemental oxygen requirement with exercise, or
- pre-menopausal and one of the following (if post-menopausal, must have a VEGF-D level ≥ 600 pg/ml and one of the following) baseline diffusing capacity for carbon monoxide ≤80% predicted,
- baseline residual volume ≥120% predicted, b) baseline desaturation by 4% or more on six minute walk testing on room air c) more than 20 cysts on the carinal cut of the CT
Who cannot join
- Existing or imminent (within 12-18 months) clinical indication for treatment with mTOR inhibitors, based on judgment of site investigator
- DLCO <60% predicted
- Resting room air saturation <90%
- Exercise induced desaturation nadir on room air < 85%
- History of myocardial infarction, angina or stroke related to atherosclerosis
- Pregnant, breast feeding, or plan to become pregnant in the next 2.5 years
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- Inadequate contraception
- Significant hematologic, renal, metabolic or hepatic abnormality (i.e. transaminase levels > three times the UL of normal range, HCT < 30%, platelets < 80,000/mm3, adjusted absolute neutrophil count < 1,000/ mm3, total WBC < 3,000/ mm3), creatinine >2.5 mg/dl, uncontrolled hyperlipidemia
- Acute or chronic infection, such as (nontuberculous mucobacteria or active hepatitis B or C infections)
- Recent surgery (involving entry into a body cavity or requiring 3 or more sutures) within three weeks of initiation of study drug
- Use of sirolimus, everolimus or investigational treatment for LAM within the 30 days prior to randomization
- Previous lung transplantation or active on transplant list
- Inability to attend scheduled clinic visits, or perform pulmonary function testing
- Pleural effusion or chylous ascites sufficient to affect pulmonary function based on the opinion of the Site Investigator
- Acute pneumothorax within the past month
- History of malignancy in the past two years, other than squamous or basal cell skin cancer.
- Use of estrogen containing medications within the 30 days prior to randomization.
- Known allergy to sirolimus
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Emory University
Atlanta, Georgia, 30322
Brigham and Woman's Hospital
Boston, Massachusetts, 20892
Loyola University
Chicago, Illinois, 60153
University of Cincinnati
Cincinnati, Ohio, 45174
National Jewish Hospital
Denver, Colorado, 80206-2761
Stanford University
Palo Alto, California, 94305
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Swedish Health
Seattle, Washington, 98104
About this study
This is a study to determine if early, long-term low dose sirolimus is effective for preventing progression to more advanced stages.
Read the detailed description
The primary objective of the MILED trial is to determine if early, long term (2 yr), low dose (fixed at 1 mg/day) treatment of patients with well-preserved lung function will prevent disease progression to more advanced stages. Sixty patients with FEV1>70% predicted will be enrolled and randomized to receive 1 mg/day sirolimus or placebo, and followed for a period of 2 years with pulmonary function testing every 4 months. The primary endpoint will be the between-group (placebo vs. sirolimus) difference in the rate of change in FEV1 (in liters) over two years. Secondary endpoints will include severity grade adverse events, time to 200cc or 10% FEV1 decline, forced vital capacity, lung volumes, diffusing capacity, serum VEGF-D, and early airflow obstruction assessed using hyper-polarized gas MRI. The study will be conducted through the Rare Lung Disease Clinic Network, a confederacy of clinics organized by the LAM Foundation that is currently following over 1300 U.S. LAM patients and conducting the Department of Defense sponsored Trial of an Aromatase Inhibitor in LAM (TRAIL) trial. The LAM Foundation will assist with study recruitment and dissemination of results, and the University of South Florida will function as the Data Coordinating Center. Successful completion of this study will define the safety and efficacy of low dose sirolimus in patients with normal lung function, and determine if sirolimus can be used to prevent disease progression to symptomatic stages.
- Conditions
- LAM, Lymphangioleiomyomatosis
- Being tested
- Sirolimus
- Medical subject headings
- Lymphangioleiomyomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin
mTOR inhibitor or placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Overencapsulated matrix Receives: Drug: Sirolimus |
| Treatment | Active comparator | Over-encapsulated 1 mg sirolimus tablet Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forced Expiratory Volume in 1 Second (FEV1 slope)
Rate of lung function decline
Measured: 2 years
Secondary outcomes (2)
Diffusing Capacity for Carbon Monoxide (DLCO)
Rate of decline in diffusing capacity
Measured: 2 years
Total Lung Capacity (TLC)
Rate of change in total lung capacity
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study start1 Jan 2018
- Primary completion30 Jun 2025 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LAMStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Intention to treat, randomized, placebo controlled, double blind
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Center for Advancing Translational Sciences (NCATS), The LAM Foundation
- Responsible party
- Principal investigator, Francis McCormack, University of Cincinnati
- Investigators
- Francis X. McCormack, M.D., Study chair, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03150914
- Sponsor's protocol ID
- RLDC5713
- Other IDs
- U01HL131755-01
- Acronym
- MILED
- Status last verified
- Dec 2024
- First submitted
- 10 May 2017
- Last updated
- 24 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be publicly available once the study in published. Deidentified data will be shared with a data use agreement between the requesting entity and the University of Cincinnati.
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Interventional Lymphangioleiomyomatosis (LAM) Early Disease Trial
- ClinicalTrials.gov ID
- NCT03150914
- Acronym / sponsor ID
- MILED / RLDC5713
- Conditions
- LAM, Lymphangioleiomyomatosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Center for Advancing Translational Sciences (NCATS), The LAM Foundation
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 12 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study to determine if early, long-term low dose sirolimus is effective for preventing progression to more advanced stages.
Detailed description
The primary objective of the MILED trial is to determine if early, long term (2 yr), low dose (fixed at 1 mg/day) treatment of patients with well-preserved lung function will prevent disease progression to more advanced stages. Sixty patients with FEV1>70% predicted will be enrolled and randomized to receive 1 mg/day sirolimus or placebo, and followed for a period of 2 years with pulmonary function testing every 4 months. The primary endpoint will be the between-group (placebo vs. sirolimus) difference in the rate of change in FEV1 (in liters) over two years. Secondary endpoints will include severity grade adverse events, time to 200cc or 10% FEV1 decline, forced vital capacity, lung volumes, diffusing capacity, serum VEGF-D, and early airflow obstruction assessed using hyper-polarized gas MRI. The study will be conducted through the Rare Lung Disease Clinic Network, a confederacy of clinics organized by the LAM Foundation that is currently following over 1300 U.S. LAM patients and conducting the Department of Defense sponsored Trial of an Aromatase Inhibitor in LAM (TRAIL) trial. The LAM Foundation will assist with study recruitment and dissemination of results, and the University of South Florida will function as the Data Coordinating Center. Successful completion of this study will define the safety and efficacy of low dose sirolimus in patients with normal lung function, and determine if sirolimus can be used to prevent disease progression to symptomatic stages.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Intention to treat, randomized, placebo controlled, double blind
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: SirolimusOverencapsulated matrix |
| Treatment | Active comparator | Drug: SirolimusOver-encapsulated 1 mg sirolimus tablet |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Female, age 18 or over
- Signed and dated informed consent
- Diagnosis of LAM as determined by compatible lung CT and one of the following
- Post-bronchodilator forced expiratory volume in one second of > 70%
- Presence of markers of non-trivial burden of LAM or likely progression based on one of the following:
Key exclusion criteria (18 listed)
- Existing or imminent (within 12-18 months) clinical indication for treatment with mTOR inhibitors, based on judgment of site investigator
- DLCO <60% predicted
- Resting room air saturation <90%
- Exercise induced desaturation nadir on room air < 85%
- History of myocardial infarction, angina or stroke related to atherosclerosis
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 |
|---|---|---|
| SirolimusAlso: RapamycinmTOR inhibitor or placebo | Drug | Placebo, Treatment |
Primary outcome
Forced Expiratory Volume in 1 Second (FEV1 slope)
Time frame: 2 years
Rate of lung function decline
2 secondary outcomes
Diffusing Capacity for Carbon Monoxide (DLCO)
Time frame: 2 years
Total Lung Capacity (TLC)
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2024.
- Individual participant dataSharing planned: Yes. Data will be publicly available once the study in published. Deidentified data will be shared with a data use agreement between the requesting entity and the University of Cincinnati.
Related trials for LAM
RecruitingPhase 1
Evaluating the Long-term Safety and Tolerability of Imatinib in Patients With Lymphangioleiomyomatosis (LAM)
Lymphangioleiomyomatosis (LAM), Lymphangioleiomyomatosis
RecruitingObservational study
Role of Extracellular Vesicles as Biomarkers of Pulmonary Involvement in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex
Lymphangioleiomyomatosis (LAM), Extracellular Vesicles; Generation and Function
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.
Francis X. McCormack, M.D. study chair
University of Cincinnati
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sirolimus in people with LAM and Lymphangioleiomyomatosis, run by University of Cincinnati at 8 sites 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 12 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 24 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Forced Expiratory Volume in 1 Second (FEV1 slope) (time frame: 2 years). 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 24 Dec 2024; AzTrials last refreshed its copy on 1 Nov 2026.