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Lymphangioleiomyomatosis Efficacy and Safety Trial


Phase 3
18 Years
N/A
Open (Enrolling)
Female
Lymphangioleiomyomatosis

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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 FoundationCleveland, Ohio  44195
Medical University of South CarolinaCharleston, South Carolina  29425-0721
University of Texas Health Center at TylerTyler, Texas  75708
National Heart, Lung, and Blood InstituteBethesda, Maryland  20892
University of California Los AngelesLos Angeles, California  90095-6951
Oregon Health & Science UniversityPortland, Oregon  97201
University Of Cincinnati Medical CenterCincinnati,, Ohio  45267-0589
National Jewish Medical and Research CenterDenver, Colorado  80401
University of Florida, GainesvilleGainesville, Florida  32611
Harvard's Brigham and Women's HospitalBoston, Massachusetts  02115