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.