Conditions: Lymphangioleiomyomatosis
Keywords: Lymphangiomyomatosis mTOR
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 89
Healthy volunteers: no

Brief summary:
Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that is caused by genetic mutations. It results in the uncontrolled growth of an unusual type of smooth muscle cell in the lung. These cells invade lung tissue, including the airways, blood vessels, and lymph vessels, and restrict the flow of air, blood, and lymph, respectively. Respiratory failure, lung collapse (pneumothorax), and pleural effusions (chylothorax) are hallmarks of the disease. This study will evaluate the safety and effectiveness of sirolimus, an inhibitor of the mTOR pathway, in stabilizing or improving lung function in people with LAM.

Detailed description:
LAM is an uncommon, progressive, cystic lung disease that predominantly affects young women. The disease is caused by mutations in tuberous sclerosis complex (TSC) genes, which regulate cellular pathways that control nutrient sensing, cell size, cell migration, and cell proliferation. Individuals with LAM often experience pneumothorax and chylothorax, as well progressive loss of lung function. Sirolimus is drug that was approved for the prevention of kidney transplant rejection. It directly affects the cellular pathway that causes LAM. This study will evaluate the safety and effectiveness of sirolimus in stabilizing or improving lung function in people with LAM.

Individuals interested in participating in this 2-year, double-blind study will first report to the study sites for pulmonary function testing to determine their eligibility for participation. Participants deemed eligible will be randomly assigned to receive either sirolimus or placebo for 1 year. Sirolimus or placebo will be administered in 2 tablet doses (2 mg for sirolimus) for the duration of the study. Study visits will occur at baseline, Week 3, every 3 months for 12 months, and months 18 and 24. Study visits will include a physical exam, questionnaires, a pregnancy test, blood and urine collection, and functional lung tests. A 6-minute walk test will occur at most study visits; a chest x-ray will be taken at baseline and month 24; and a volumetric computed tomography scan will occur at baseline, month 12, and month 24. Adverse events, medication side effects, and lung function will be assessed at each visit.

Arms:
arm 1: Participants receive sirolimus daily for 1 year and are followed with serial pulmonary function tests, 6-minute walk tests, and symptom and QOL questionnaires over a 2-year period. arm 2: Participants receive placebo daily for 1 year and followed with serial pulmonary function tests, 6-minute walk tests, and symptom and QOL questionnaires over a 2-year period.

Interventions: intervention 1: Sirolimus intervention 2: Placebo
Intervention descriptions: intervention 1: A sirolimus dose of 2 tablets (1 mg/tablet) per day for 1 year. intervention 2: A placebo dose of 2 tablets per day for 1 year.

Protocol document: