Overview

This trial is active, not recruiting.

Condition lymphangioleiomyomatosis
Treatments sirolimus, placebo sirolimus
Phase phase 3
Target mTOR
Sponsor Office of Rare Diseases (ORD)
Collaborator FDA Office of Orphan Products Development
Start date December 2006
End date September 2010
Trial size 120 participants
Trial identifier NCT00414648, 1 U54 RR019498-01, NCT00408343, NCT00720746, RDCRN 5702, RLD 5702

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Participants will receive sirolimus daily for 1 year followed with serial pulmonary functional tests and 6-minute walk tests over a 2-year period.
sirolimus Rapamycin
A sirolimus dose of 2 mg will be given in the form of 2 tablets (1 mg/tablet) per day for 1 year.
(Placebo Comparator)
Participants will receive placebo sirolimus daily for 1 year followed with serial pulmonary functional tests and 6-minute walk tests over a 2-year period.
placebo sirolimus Other names: placebo
A placebo dose of 2 mg will be given in the form of 2 tablets (1 mg/tablet) per day for 1 year.

Primary Outcomes

Measure
FEV1 response
time frame: measured at Month 12
Severity graded adverse events
time frame: measured at Month 12

Secondary Outcomes

Measure
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

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Age 18 or older - Diagnosis of LAM as determined by a biopsy and chest CT scan; or chest CT scan in the setting of tuberous sclerosis, angiomyomata or chylous pleural effusion; or chest CT scan and a VEGF-D level of at least 800 pg/ml - Forced expiratory volume in one second (FEV1) of 70% or less of predicted value after administration of a bronchodilator Exclusion Criteria: - Known allergy to sirolimus - History of heart attack, angina, or stroke due to clogging, narrowing, and hardening of the arteries and blood vessels - Significant hematologic or hepatic abnormality (transaminase levels greater than three times the upper limit of normal, HCT less than 30%, platelets less than 80,000/cubic mm, adjusted absolute neutrophil count less than 1,000/cubic mm, total white blood cell count less than 3,000/cubic mm) - Intercurrent infection at the time treatment with sirolimus begins - Any surgery involving entry into a body cavity or requiring three or more sutures within 8 weeks of initiation of study drug - Use of an investigational drug within the 30 days prior to random assignment - Uncontrolled hyperlipidemia - Previous lung transplant or currently on lung transplant list - Unable to attend scheduled study visits - Unable to perform pulmonary function tests - Creatinine levels greater than 2.5 mg/dl - Chylous ascites severe enough to affect diaphragmatic function - Pleural effusion severe enough to affect pulmonary function, as determined by the study physician - History of acute pneumothorax within the 2 months prior to study entry - History of malignancy within the 2 years prior to study entry (except for squamous or basal cell skin cancer) - Use of estrogen containing medication within the thirty days prior to randomization - Unable or unwilling to use adequate contraception - Pregnant, breastfeeding, or plans to become pregnant within the next 2 years

Additional Information

Official title Lymphangioleiomyomatosis Efficacy and Safety Trial
Principal investigator Frank McCormack, MD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2009.
Information provided to ClinicalTrials.gov by Office of Rare Diseases (ORD).