Clinical Trial: Efficacy and Safety of Sirolimus for Treating Lymphangioleiomyomatosis (LAM)

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Lymphangioleiomyomatosis Efficacy and Safety Trial

Brief Summary: Lymphangioleiomyomatosis (LAM) is a rare lung disease that is caused by genetic mutations. It results in the uncontrolled growth and proliferation of an unusual type of smooth muscle cell. 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 immunosuppressive medication, in stabilizing or improving lung function in people with LAM.

Detailed Summary:

LAM is an uncommon, progressive, cystic lung disease that predominantly affects young women. It is believed to be caused by defects within cellular pathways that regulate nutrient uptake, cell size, cell migration, and cell proliferation. The disease is caused by mutations in tuberous sclerosis complex (TSC) genes. Individuals with LAM often experience pneumothorax and chylothorax, as well progressive loss of lung function. LAM is frequently fatal and existing therapies for the disease have not proven effective. Lung transplantation can be considered as a last option, but alternative treatments are needed. Sirolimus is an immunosuppressive drug that is often used in people who have had kidney transplants. It directly affects the genetic 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.


Sponsor: Office of Rare Diseases (ORD)

Current Primary Outcome:

  • FEV1 response [ Time Frame: measured at Month 12 ]
  • Severity graded adverse events [ Time Frame: measured at Month 12 ]


Original Primary Outcome:

  • FEV1 response
  • Adverse events (measured at 1 year)


Current Secondary Outcome:

  • FVC response [ Time Frame: measured at Month 24 ]
  • Diffusing capacity for carbon monoxide [ Time Frame: measured at Month 24 ]
  • Lung volume [ Time Frame: measured at Month 24 ]
  • Distance walked in 6 minutes [ Time Frame: measured at Month 24 ]
  • Volumetric estimate of lung cyst size and mass of tissue in the chest [ Time Frame: measured at Month 24 ]
  • Biomarkers [ Time Frame: measured at Month 24 ]
  • Chylous effusions [ Time Frame: measured at Month 24 ]
  • Pneumothoraces [ Time Frame: measured at Month 24 ]
  • Hemorrhagic renal episodes [ Time Frame: measured at Month 24 ]
  • Mortality [ Time Frame: measured at Month 12 ]


Original Secondary Outcome:

  • FVC response
  • Diffusing capacity for carbon monoxide
  • Lung volume
  • Distance walked in 6 minutes
  • Volumetric estimate of lung cyst size and mass of tissue in the chest
  • Biomarkers
  • Chylous effusions
  • Pneumothoraces
  • Hemorrhagic renal episodes
  • Mortality (measured at 1 year)


Information By: Office of Rare Diseases (ORD)

Dates:
Date Received: December 20, 2006
Date Started: December 2006
Date Completion: September 2011
Last Updated: August 27, 2009
Last Verified: August 2009