Clinical trial NCT02432560: Safety and Durability of Sirolimus for Treatment of LAM
Official title: Multicenter International Durability and Safety of Sirolimus in LAM Trial (MIDAS)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lymphangioleiomyomatosis
Keywords: Lymphangioleiomyomatosis
LAM
rare lung
Rare Lung Disease
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: Rare Diseases Clinical Research Network
name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: The LAM Foundation
First posted: 2015-05-04
Enrollment: 600
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Rare Lung Disease Clinical Network Consortium Clinics

Brief summary: The MIDAS study aims to follow male and female 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.

Detailed 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. There is therefore a need to understand 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, real world registry. 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 that are obtained for clinical purposes over periods of at least 2 years. The decision to treat with mTOR inhibitor therapy is made by the clinician and the patient, and will be managed by the participant's clinician. 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 NIH/NCATS Rare Lung Disease Consortium, with data stored and analyzed by the Database Management Coordinating Center (DMCC) at the University of South Florida.

Eligibility criteria: Inclusion Criteria:

* Female or male, age 18 or over
* Diagnosis of LAM based on ATS/JRS criteria
* 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

Primary outcomes:
measure: Long term safety of mTOR inhibitor treatment in LAM
timeFrame: 2-5 years
measure: Efficacy - FEV1 slope
timeFrame: 2-5 years
measure: Efficacy -10% reduction in FEV1
timeFrame: 2-5 years
Secondary outcomes:
measure: Effect of long term sirolimus on quality of life
timeFrame: 2-5 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center, Chicago
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine
state: Utah
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: University of Cincinnati
name: Francis X McCormack, MD
role: STUDY_DIRECTOR
References: