Multicenter Interventional Lymphangioleiomyomatosis (LAM) Early Disease Trial

Summary

Objectives

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.