Trial of Aromatase Inhibition in Lymphangioleiomyomatosis (TRAIL)
The hypothesis in this study is that estrogen suppression by an aromatase inhibitor in postmenopausal women with Lymphangioleiomyomatosis (LAM) will prevent or delay progression of lung disease and result in a decrease in the rate of decline in FEV1
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Trial of Letrozole in Pulmonary Lymphangioleiomyomatosis With or Without Measurable Tumors or Lymph Nodes|
- The effect on Forced Expiratory Volume in one second [ Time Frame: twelve months ] [ Designated as safety issue: No ]
- Other measures of pulmonary function [ Time Frame: twelve months ] [ Designated as safety issue: No ]FVC, DLCO, TLC,RV, FRC, 6MWT
- Quality of life measures [ Time Frame: twelve months ] [ Designated as safety issue: No ]Quality of Life, dyspnea and fatigue, functional performance
- Serum VEGF-D [ Time Frame: twelve months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2011|
|Estimated Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
2.5 mg daily for twelve months
Other Name: Femara
|Placebo Comparator: Placebo||
sugar pill given daily for twelve months
Lymphangioleiomyomatosis, or LAM, is an uncommon, progressive, cystic lung disease that predominantly affects young women. Pulmonary parenchymal changes consistent with LAM are found in about one third of women with tuberous sclerosis complex (TSC), an autosomal dominant tumor suppressor syndrome. LAM also occurs in a sporadic form that is not associated with germ line mutations in TSC genes. Recent evidence that recurrent LAM after lung transplantation results from seeding of the graft from a remote source and suggests a metastatic mechanism for the disease.
Since LAM occurs almost exclusively in women, and exposure to estrogen either exogenously or during pregnancy can exacerbate LAM, estrogen suppression might be expected to prevent or delay progression of disease. In preclinical studies, estrogen induces the growth of TSC2-deficient cells and tumor cells derived from LAM patients. In a xenograft model of lymphangioleiomyomatosis presented by Dr. Yu at the 2008 LAM Research Meeting, estrogen promoted the pulmonary metastases of tuberin-deficient ELT3 cells (TSC2-deficient rat uterine leiomyoma cells) in female ovariectomized CB-17-scid mice, while the estrogen inhibitor fulvestrant completely blocked estrogen-promoted pulmonary metastases. This work was recently published.
Letrozole is a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis)(14). It is chemically described as 4,4'-(1H-1,2,4-Triazol-1-ylmethylene)diben-zonitrile.
In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase enzyme.
|Contact: Francis X McCormack, MDemail@example.com|
|Contact: Tammy Roads, CRCfirstname.lastname@example.org|
|United States, Ohio|
|University of Cincinnati||Recruiting|
|Cincinnati, Ohio, United States, 45267|
|Contact: Deborah M Conradi, RN 513-558-0027 email@example.com|
|Contact: Tammy Roads, CRC 513-558-2148 firstname.lastname@example.org|
|Principal Investigator: Francis X McCormack, MD|
|Sub-Investigator: Lisa R Young, MD|
|Principal Investigator:||Francis X McCormack, MD||University of Cincinnati|