Trial of Letrozole in Lymphangioleiomyomatosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 9
- 主要终点
- Rate of Change in Forced Expiratory Volume in 1 Second in ml/Month
研究概览
简要总结
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
详细描述
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 germline 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 is exacerbated by pregnancy, menses and hormonal therapies suggest that estrogen suppression might be expected to prevent or delay progression of disease.
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 can therefore be achieved by specifically inhibiting the aromatase enzyme. Letrozole is a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis) that has been shown to be effective in other neoplasms that affect women, such as breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Definite diagnosis of based on compatible chest CT and at least one of the following:
- •biopsy or cytology consistent with LAM, or
- •tuberous sclerosis, renal angiomyolipoma, cystic abdominal lymphangiomas, or chylous effusion in the chest or abdomen, or
- •serum VEGF-D ≥ 800 pg/uL.
- •post bronchodilator FEV1 ≤80% predicted or DLCO ≤70% predicted or RV≥120% predicted
- •female and postmenopausal status as defined by one of the following:
- •prior bilateral oophorectomy or bilateral ovarian irradiation, or
- •age greater than 55 years, and no menstrual period for 12 months or longer.
- •age 18-55 years and estradiol level in the postmenopausal range in the absence of current use of progestational agents.
- •If still premenopausal, may enter if rendered medically postmenopausal on clinical grounds with the use of gonadotropin releasing hormone (e.g. leuprolide), as long as serum estradiol, FSH, and LH are in the postmenopausal range
- •Patients with osteopenia or osteoporosis must be receiving appropriate treatment for their osteoporosis or osteopenia at entry into this study.
排除标准
- •Known allergy to letrozole
- •Inability to comply with pulmonary function tests or follow up visits.
- •Treatment with investigational agents within 30 days
- •Hormonal therapy (e.g. estrogen, progestin, LHRH agonists or antagonists, estrogen receptor blockers, estrogen receptor down regulators, aromatase inhibitors) within 30 days month of registration
- •Medical or psychiatric conditions that would interfere with the ability to provide informed consent.
- •abnormal hematologic and hepatic function as defined by the following at the time of randomization.:
- •Neutrophils < 1500/mm3 and platelets < 100,000/mm3
- •Bilirubin < 1.25 X upper limit of normal
- •SGPT (ALT) or SGOT (AST) >2.5 X upper limit of normal
研究组 & 干预措施
Letrozole
Patients are placed on letrozole, 1 tablet (2.5 mg) daily for one year
干预措施: Letrozole (Drug)
Placebo
Patients are placed on placebo, 1 tablet daily for one year
干预措施: Placebo (Drug)
结局指标
主要结局
Rate of Change in Forced Expiratory Volume in 1 Second in ml/Month
时间窗: 12 months
FEV1 values reported are in liters or milliliters. There are no definite minimum and maximum values of FEV1 as it is a physiological measure of lung function and varies from individual to individual. Higher FEV1 scores indicate better lung function.
次要结局
- Post-bronchodilator FVC(twelve months)
- St George Respiratory Questionnaire(twelve months)
- Serum VEGF-D(twelve months)
研究者
Francis McCormack
Professor and Director, Pulmonary, Critical Care and Sleep Medicine
University of Cincinnati