Safety and Durability of Sirolimus for Treatment of LAM

Lymphangioleiomyomatosis Clinical Trial

— MIDAS  

Official title:

Multicenter International Durability and Safety of Sirolimus in LAM Trial (MIDAS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02432560
• Other study ID #: MIDAS
• Secondary ID: 1U54HL127672
• Status: Recruiting
• Start date: March 2015
• Est. completion date: August 2024

Study information

• Verified date: January 2022
• Source: University of Cincinnati
• Contact: Susan McMahan Sellers, BSN, RN
• Phone: (513) 558-4376
• Email: susan.mcmahan[@]uc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The MIDAS study aims to follow LAM patients who are currently taking, have previously failed or been intolerant of, or may (at some time in the future) take mTOR inhibitors (sirolimus or everolimus) as part of their clinical care. Adult female TSC patients may also enroll, with or without lung cysts.

Description:

Lymphangioleiomyomatosis (LAM) is an uncommon disease affecting women. It is associated with cystic lung destruction and progressive respiratory failure. The Multicenter International LAM Efficacy of Sirolimus (MILES) Trial, led by the investigators' research team, demonstrated that mTOR (mammalian target of rapamycin) inhibition with sirolimus was an effective therapy that stabilized decline in FEV1 (forced expiratory volume). However, lung function decline resumed when the drug was stopped at the one year point in MILES, suggesting that therapy is suppressive rather than remission-inducing, and may need to be lifelong. The investigators therefore need to know whether long-term therapy with sirolimus is safe and effective. To accomplish this goal, the investigators will conduct the Multicenter International Durability and Safety of Sirolimus in LAM Trial (MIDAS). This is an observational "registry" trial. The investigators propose to enroll 600 LAM patients who are on, have previously failed or been intolerant of or are considering taking sirolimus or everolimus for clinical reasons in a longitudinal observational study. This registry will follow lung function tests and adverse events over periods of at least 2 years. The mTOR inhibitor therapy will be initiated and managed by the participant's clinician. The study is planned to use the collected data from standard of care. This study will help us to refine treatment for patients with LAM and determine if long term suppressive therapy with sirolimus can prevent progression to later stages of disease. This research will be accomplished as part of the Rare Lung Disease Clinical Network Consortium, with data stored and analyzed by the Database Management Coordinating Center (DMCC) as part of the NIH-supported Rare Disease Consortium.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: August 2024
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female, age 18 or over
• Diagnosis of LAM
• Signed and dated informed consent
• On chronic therapy, newly treated or may be considered for therapy with mTOR inhibitors or previously intolerant of or having failed mTOR inhibitor therapy

Exclusion Criteria:

• Inability to attend at least one RLD Clinic visit per year
• Inability to give informed consent
• Inability or unwillingness to perform pulmonary function testing

Related Conditions & MeSH terms

• Lymphangioleiomyomatosis

Intervention

Drug:
• Sirolimus
Sirolimus treatment will be part of a participant's clinical care and will be managed by their physician.
• Everolimus
Everolimus treatment will be part of a participant's clinical care and will be managed by their physician.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	University of Texas Health Center	Houston	Texas
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Loyola University Medical Center, Chicago	Maywood	Illinois
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah School of Medicine	Salt Lake City	Utah
United States	Swedish Medical Center	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California

Sponsors (5)

Lead Sponsor	Collaborator
University of Cincinnati	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Rare Diseases Clinical Research Network, The LAM Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Long term safety of mTOR inhibitor treatment in LAM	Subjects will report symptoms experienced during the observation period on sirolimus/everolimus therapy	2 years
Primary	Efficacy - FEV1 slope	forced expiratory volume (FEV1) slope over 2 years	2 years
Primary	Efficacy -10% reduction in FEV1	time to 10% reduction in FEV1	2 years
Primary	Efficacy - 10% reduction in FVC1	time to 10% reduction in FVC (forced vital capacity) as compared to the placebo group from the MILES trial	2 years
Primary	Efficacy - annual change in spirometry	absolute annual change in spirometry [FEV1, FVC, TLC (total lung capacity), RV (residual volume) and diffusing capacity]	2 years
Secondary	Effect of long term sirolimus on quality of life	Evaluate ATAQ-LAM QOL responses over time	2 years