Lymphangioleiomyomatosis Efficacy and Safety Trial
18 Years
N/A
Female
Lymphangioleiomyomatosis
Trial Information
Lymphangioleiomyomatosis Efficacy and Safety Trial
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment
Outcome Measure:
FEV1 response
Outcome Time Frame:
measured at Month 12
Safety Issue:
No
Principal Investigator
Frank McCormack, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Cincinnati Medical Center Division of Pulmonary and Critical Care Medicine
Authority:
United States: Federal Government
Study ID:
RDCRN 5702
NCT ID:
NCT00414648
Start Date:
December 2006
Completion Date:
September 2011
Related Keywords:
- Lymphangioleiomyomatosis
- Lymphangiomyomatosis
- Lung Disease
- Lymphangioleiomyomatosis
Name | Location |
|---|---|
| Cleveland Clinic Foundation | Cleveland, Ohio 44195 |
| Medical University of South Carolina | Charleston, South Carolina 29425-0721 |
| University of Texas Health Center at Tyler | Tyler, Texas 75708 |
| National Heart, Lung, and Blood Institute | Bethesda, Maryland 20892 |
| University of California Los Angeles | Los Angeles, California 90095-6951 |
| Oregon Health & Science University | Portland, Oregon 97201 |
| University Of Cincinnati Medical Center | Cincinnati,, Ohio 45267-0589 |
| National Jewish Medical and Research Center | Denver, Colorado 80401 |
| University of Florida, Gainesville | Gainesville, Florida 32611 |
| Harvard's Brigham and Women's Hospital | Boston, Massachusetts 02115 |
