Clinical Trial: Safety and Durability of Sirolimus for Treatment of LAM

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

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

Brief Summary: The MIDAS study aims to follow women with LAM who are currently taking, have previously failed or been intolerant of, or are considering treatment with mTOR inhibitors sirolimus or everolimus as part of their clinical care.

Detailed Summary: 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 300 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.
Sponsor: Children's Hospital Medical Center, Cincinnati

Current Primary Outcome:

  • Safety (subjects will collect symptoms in diary) [ Time Frame: 2 years ]
    subjects will collect symptoms in diary
  • Efficacy - FEV1 slope [ Time Frame: 2 years ]
    forced expiratory volume (FEV1) slope over 2 years
  • Efficacy -10% reduction in FEV1 [ Time Frame: 2 years ]
    time to 10% reduction in FEV1
  • Efficacy - 10% reduction in FVC1 [ Time Frame: 2 years ]
    time to 10% reduction in FVC (forced vital capacity) as compared to the placebo group from the MILES trial
  • Efficacy - annual change in spirometry [ Time Frame: 2 years ]
    absolute annual change in spirometry [FEV1, FVC, TLC (total lung capacity), RV (residual volume) and diffusing capacity]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Quality of Life [ Time Frame: 2 years ]
    Euro VAS Scale for QoL, Fatigue, and Dyspnea, Shortness of Breath Questionnaire, ATAQ-LAM Questionnaire
  • Functional Performance (St. George's Respiratory Questionnaire, Functional Performance Inventory) [ Time Frame: 2 years ]
    St. George's Respiratory Questionnaire, Functional Performance Inventory


Original Secondary Outcome: Same as current

Information By: Children's Hospital Medical Center, Cincinnati

Dates:
Date Received: March 4, 2015
Date Started: March 2015
Date Completion: April 2020
Last Updated: May 1, 2015
Last Verified: April 2015