Safety and Durability of Sirolimus for Treatment of LAM (MIDAS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphangioleiomyomatosis
• Intervention / Treatment: Drug: Everolimus; Drug: Sirolimus

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. 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.

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

• Study Contact: Name: Susan McMahan Sellers, BSN, RN; Phone Number: (513) 558-4376; Email: susan.mcmahan@uc.edu
• Study Contact Backup: Name: Francis X McCormack, MD; Phone Number: (513) 558-0588; Email: frank.mccormack@uc.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University Medical Center
      • Contact: Stephen Ruoss, MD; Phone Number: 650-723-6381; Email: ruoss@stanford.edu
  • Colorado
    • Denver, Colorado, United States, 80206
      • Recruiting
      • National Jewish Health
      • Contact: Gregory Downey, MD; Phone Number: 1881 303-398-1436; Email: gregory.downey@gmail.com
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Jacksonville
      • Contact: Charles Burger, MD; Phone Number: 904-953-2381; Email: charles.burger@mayo.edu
  • Georgia
    • Atlanta, Georgia, United States, 33136
      • Recruiting
      • Emory University School of Medicine
      • Contact: Sirhari Veeraraghavan, MD; Email: veeraraghavan@emory.edu
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Active, not recruiting
      • Loyola University Medical Center, Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Elizabeth Henske, MD; Phone Number: 857-307-0784; Email: ehenske@partners.org
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Mei Lan Han, MD; Phone Number: 734-936-5047; Email: mrking@umich.edu
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Active, not recruiting
      • Mayo Clinic Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Adrian Shifren, MD; Phone Number: 314-362-6904; Email: ashifren@wustl.edu
  • New York
    • Rochester, New York, United States, 14642-8692
      • Recruiting
      • University of Rochester Medical Center
      • Contact: MaryAnne Morgan, MD; Phone Number: 585-275-4161; Email: maryanne_morgan@urmc.rochester.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Active, not recruiting
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Active, not recruiting
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Active, not recruiting
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Active, not recruiting
      • University of Pennsylvania Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Active, not recruiting
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232-2650
      • Active, not recruiting
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Active, not recruiting
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • University of Texas Health Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Active, not recruiting
      • University of Utah School of Medicine
  • Washington
    • Seattle, Washington, United States, 98104
      • Active, not recruiting
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Rare Lung Disease Clinical Network Consortium Clinics

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Everolimus; women over age 18 who have LAM and are currently taking, have previously failed or been intolerant of, or who are considering taking everolimus as part of their clinical care	Drug: Everolimus; Everolimus treatment will be part of a participant's clinical care and will be managed by their physician.; Other Names: Afinitor
Sirolimus; women over age 18 who have LAM and are currently taking, have previously failed or been intolerant of, or who are considering taking sirolimus as part of their clinical care	Drug: Sirolimus; Sirolimus treatment will be part of a participant's clinical care and will be managed by their physician.; Other Names: Rapamune, rapamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long term safety of mTOR inhibitor treatment in LAM	Subjects will report symptoms experienced during the observation period on sirolimus/everolimus therapy	2 years
Efficacy - FEV1 slope	forced expiratory volume (FEV1) slope over 2 years	2 years
Efficacy -10% reduction in FEV1	time to 10% reduction in FEV1	2 years
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of long term sirolimus on quality of life	Evaluate ATAQ-LAM QOL responses over time	2 years

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); The LAM Foundation; Rare Diseases Clinical Research Network
• Investigators: Study Director: Francis X McCormack, MD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2024

Study Registration Dates

• First Submitted: March 4, 2015
• First Submitted That Met QC Criteria: May 1, 2015
• First Posted (Estimate): May 4, 2015

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: LAM; Lymphangioleiomyomatosis; rare lung; Rare Lung Disease
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphangiomyoma; Lymphatic Vessel Tumors; Perivascular Epithelioid Cell Neoplasms; Lymphangioleiomyomatosis; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Everolimus; Sirolimus
• Other Study ID Numbers: MIDAS; 1U54HL127672 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No