Efficacy and Safety of Sirolimus for Treating Lymphangioleiomyomatosis (LAM)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by Office of Rare Diseases (ORD).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:
NCT00414648
First received: December 20, 2006
Last updated: August 27, 2009
Last verified: August 2009

December 20, 2006
August 27, 2009
December 2006
September 2010   (final data collection date for primary outcome measure)
  • FEV1 response [ Time Frame: measured at Month 12 ] [ Designated as safety issue: No ]
  • Severity graded adverse events [ Time Frame: measured at Month 12 ] [ Designated as safety issue: Yes ]
  • FEV1 response
  • Adverse events (measured at 1 year)
Complete list of historical versions of study NCT00414648 on ClinicalTrials.gov Archive Site
  • FVC response [ Time Frame: measured at Month 24 ] [ Designated as safety issue: No ]
  • Diffusing capacity for carbon monoxide [ Time Frame: measured at Month 24 ] [ Designated as safety issue: No ]
  • Lung volume [ Time Frame: measured at Month 24 ] [ Designated as safety issue: No ]
  • Distance walked in 6 minutes [ Time Frame: measured at Month 24 ] [ Designated as safety issue: No ]
  • Volumetric estimate of lung cyst size and mass of tissue in the chest [ Time Frame: measured at Month 24 ] [ Designated as safety issue: No ]
  • Biomarkers [ Time Frame: measured at Month 24 ] [ Designated as safety issue: No ]
  • Chylous effusions [ Time Frame: measured at Month 24 ] [ Designated as safety issue: Yes ]
  • Pneumothoraces [ Time Frame: measured at Month 24 ] [ Designated as safety issue: Yes ]
  • Hemorrhagic renal episodes [ Time Frame: measured at Month 24 ] [ Designated as safety issue: Yes ]
  • Mortality [ Time Frame: measured at Month 12 ] [ Designated as safety issue: Yes ]
  • 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)
Not Provided
Not Provided
 
Efficacy and Safety of Sirolimus for Treating Lymphangioleiomyomatosis (LAM)
Lymphangioleiomyomatosis Efficacy and Safety Trial

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Lymphangioleiomyomatosis
  • Drug: Sirolimus
    A sirolimus dose of 2 mg will be given in the form of 2 tablets (1 mg/tablet) per day for 1 year.
    Other Name: Rapamycin
  • Drug: Placebo sirolimus
    A placebo dose of 2 mg will be given in the form of 2 tablets (1 mg/tablet) per day for 1 year.
    Other Name: Other names: placebo
  • Experimental: 1
    Participants will receive sirolimus daily for 1 year followed with serial pulmonary functional tests and 6-minute walk tests over a 2-year period.
    Intervention: Drug: Sirolimus
  • Placebo Comparator: 2
    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.
    Intervention: Drug: Placebo sirolimus

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
120
September 2011
September 2010   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Japan
 
NCT00414648
RDCRN 5702, RLD 5702, 1 U54 RR019498-01
Yes
Frank McCormack, MD, University of Cincinnati Medical Center
Office of Rare Diseases (ORD)
FDA Office of Orphan Products Development
Principal Investigator: Frank McCormack, MD University of Cincinnati Medical Center Division of Pulmonary and Critical Care Medicine
Principal Investigator: Bruce Trapnell, MD Cincinnati Children's Hospital Medical Center Division of Pulmonary Biology
Office of Rare Diseases (ORD)
August 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP