Multicenter Interventional Lymphangioleiomyomatosis (LAM) Early Disease Trial (MILED)

December 18, 2024 updated by: Francis McCormack, University of Cincinnati
This is a study to determine if early, long-term low dose sirolimus is effective for preventing progression to more advanced stages.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305
        • Stanford University
    • Colorado
      • Denver, Colorado, United States, 80206-2761
        • National Jewish Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60153
        • Loyola University
    • Massachusetts
      • Boston, Massachusetts, United States, 20892
        • Brigham and Woman's Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45174
        • University of Cincinnati
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Female, age 18 or over
  2. Signed and dated informed consent

  3. Diagnosis of LAM as determined by compatible lung CT and one of the following

    1. biopsy (lung, abdominal mass, lymph node or kidney) or cytology from thoracic or abdominal sources revealing LAM, or
    2. tuberous sclerosis, angiomyolipomata (diagnosed by CT, MRI by the site radiologist or biopsy) or chylous pleural effusion (verified by tap), or
    3. VEGF-D level ≥ 800 pg/ml.
  4. Post-bronchodilator forced expiratory volume in one second of > 70%

  5. Presence of markers of non-trivial burden of LAM or likely progression based on one of the following:

    1. pretrial FEV 1 rate of decline of >60cc/yr, comparing enrollment FEV1 to any prior measurement in the past 3 years, or
    2. baseline supplemental oxygen requirement with exercise, or
    3. 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,

a) 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

Exclusion Criteria:

  1. Existing or imminent (within 12-18 months) clinical indication for treatment with mTOR inhibitors, based on judgment of site investigator
  2. DLCO <60% predicted
  3. Resting room air saturation <90%
  4. Exercise induced desaturation nadir on room air < 85%
  5. History of myocardial infarction, angina or stroke related to atherosclerosis
  6. Pregnant, breast feeding, or plan to become pregnant in the next 2.5 years
  7. Inadequate contraception
  8. 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
  9. Acute or chronic infection, such as (nontuberculous mucobacteria or active hepatitis B or C infections)
  10. Recent surgery (involving entry into a body cavity or requiring 3 or more sutures) within three weeks of initiation of study drug
  11. Use of sirolimus, everolimus or investigational treatment for LAM within the 30 days prior to randomization
  12. Previous lung transplantation or active on transplant list
  13. Inability to attend scheduled clinic visits, or perform pulmonary function testing
  14. Pleural effusion or chylous ascites sufficient to affect pulmonary function based on the opinion of the Site Investigator
  15. Acute pneumothorax within the past month
  16. History of malignancy in the past two years, other than squamous or basal cell skin cancer.
  17. Use of estrogen containing medications within the 30 days prior to randomization.
  18. Known allergy to sirolimus

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Overencapsulated matrix
Drug: Sirolimus
mTOR inhibitor or placebo
Other Names:
  • Rapamycin
Active Comparator: Treatment
Over-encapsulated 1 mg sirolimus tablet
Drug: Sirolimus
mTOR inhibitor or placebo
Other Names:
  • Rapamycin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Forced Expiratory Volume in 1 Second (FEV1 slope)
Time Frame: 2 years
Rate of lung function decline
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Diffusing Capacity for Carbon Monoxide (DLCO)
Time Frame: 2 years
Rate of decline in diffusing capacity
2 years
Total Lung Capacity (TLC)
Time Frame: 2 years
Rate of change in total lung capacity
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Cincinnati

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
The LAM Foundation
National Center for Advancing Translational Sciences (NCATS)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Francis X. McCormack, M.D., University of Cincinnati

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2018

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 10, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 12, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RLDC5713
  • U01HL131755-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

Estimated Spring 2026

IPD Sharing Access Criteria

After study completion and publication, deidentified data may be requested by an email to the PI, Frank McCormack, with a data use agreement between the University of Cincinnati and the requesting entity.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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