# Multicenter Interventional Lymphangioleiomyomatosis Early Disease Trial (MILED)-CCC

> **NIH NIH U01** · UNIVERSITY OF CINCINNATI · 2021 · $536,596

## Abstract

Multicenter Interventional Lymphangioleiomyomatosis Early Disease Trial (The MILED Trial)
Project Summary
Lymphangioleiomyomatosis (LAM) is low-grade metastasizing neoplasm of women, driven by activating
mutations in the mTOR pathway that result in cystic destruction of the lung. The benign appearing, mutation
bearing smooth muscle-like LAM cells that infiltrate the lung arise from an unknown source and execute a
program of matrix remodeling that leads to cyst formation, recurrent pneumothorax, chylous pleural effusion and
progressive respiratory failure. There has been tremendous progress in LAM in the past decade, including a
rich molecular understanding of disease pathogenesis, development of a diagnostic and prognostic biomarker,
and the discovery of a treatment. The randomized controlled Rare Lung Disease Consortium (RLDC) Multicenter
International LAM Efficacy of Sirolimus (MILES) Trial (Sponsor-FXM, IND 71,340) demonstrated that mTOR
inhibition with sirolimus is an effective suppressive therapy for LAM, stabilizing lung function, functional
performance, and quality of life in women with abnormal lung function. Side effects due to sirolimus were
common in MILES, although SAEs were balanced in the sirolimus and placebo groups. The beneficial effects of
sirolimus waned when the drug was held in the second year of the trial. Although the primary eligibility criterion
was forced expiratory volume in 1 second (FEV1) ≤ 70%, enrolled MILES patients had more advanced
respiratory impairment, with about half of lung function remaining (on average), limiting the generalizability of the
findings to mild disease. Fear of toxicities and life long therapy lead most clinicians and patients to wait until lung
function becomes abnormal before initiating sirolimus therapy to stabilize the damaged lung. This approach is
suboptimal and inadequate. The Multicenter Interventional LAM Early Disease Trial (MILED) is a phase III,
randomized, placebo-controlled trial to determine if early, long term (2 yr), low dose (1 mg/day) sirolimus
treatment of patients with well-preserved lung function will safely prevent disease progression. Sixty patients
with normal FEV1 (FEV1>70%) will be enrolled and randomized to 1 mg/day sirolimus or placebo, and followed
for 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). Secondary endpoints will include
between group differences in adverse events, 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
using the infrastructure created for the RLDC, using the Rare Lung Disease Clinic Network, which is currently
following over 1200 U.S. LAM patients and conducting the TRAIL trial. The LAM Foundation will be an integral
partner and will assist with study recruitment and patient participation. Data...

## Key facts

- **NIH application ID:** 10219338
- **Project number:** 5U01HL131755-05
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Francis Xavier McCormack
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $536,596
- **Award type:** 5
- **Project period:** 2016-09-20 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219338

## Citation

> US National Institutes of Health, RePORTER application 10219338, Multicenter Interventional Lymphangioleiomyomatosis Early Disease Trial (MILED)-CCC (5U01HL131755-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10219338. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*