Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01353209
Other study ID # 5708
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date May 2011
Est. completion date September 2014

Study information

Verified date April 2024
Source University of Cincinnati
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 17
Est. completion date September 2014
Est. primary completion date September 2014
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility Inclusion Criteria: - Definite diagnosis of based on compatible chest CT and at least one of the following: 1. biopsy or cytology consistent with LAM, or 2. tuberous sclerosis, renal angiomyolipoma, cystic abdominal lymphangiomas, or chylous effusion in the chest or abdomen, or 3. 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: 1. prior bilateral oophorectomy or bilateral ovarian irradiation, or 2. age greater than 55 years, and no menstrual period for 12 months or longer. 3. 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. Exclusion Criteria: - 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Letrozole
2.5 mg daily for twelve months
Placebo
placebo given daily for twelve months

Locations

Country Name City State
United States Emory University School of Medicine Atlanta Georgia
United States University of Cincinnati Cincinnati Ohio
United States Cleveland Clinic Cleveland Ohio
United States Mayo Clinic Jacksonville Florida
United States Loyola University Medical Center Maywood Illinois
United States University of Miami Miami Florida
United States Washington University School of Medicine Saint Louis Missouri
United States Minor and James Seattle Washington
United States Stanford University Medical Center Stanford California

Sponsors (2)

Lead Sponsor Collaborator
University of Cincinnati United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lu C, Lee HS, Pappas GP, Dilling DF, Burger CD, Shifren A, Veeraraghavan S, Chapman JT, Parambil J, Ruoss SJ, Young LR, Hammes SR, Kopras EJ, Roads T, Krischer JP, McCormack FX; Trial of an Aromatase Inhibitor in Lymphangioleiomyomatosis Group. A Phase II — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Rate of Change in Forced Expiratory Volume in 1 Second in ml/Month 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. 12 months
Secondary Post-bronchodilator FVC Post-bronchodilator FVC in milliliters twelve months
Secondary St George Respiratory Questionnaire Quality of Life scale for respiratory symptoms. This is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating worse quality of life. twelve months
Secondary Serum VEGF-D VEGF-D values represent serum VEGF-D levels in pg/ml. Higher levels of VEGF-D are associated with Lymphangioleiomyomatosis. A serum VEGF-D greater than 400 pg/ml is a diagnostic biomarker for LAM. twelve months
See also
  Status Clinical Trial Phase
Completed NCT01687179 - Safety Study of Sirolimus and Hydroxychloroquine in Women With Lymphangioleiomyomatosis Phase 1
Completed NCT00366509 - Role of Helicobacter Pylori and Its Toxins in Lung and Digestive System Diseases
Completed NCT00552955 - Effect of Fasting on the Size of Abdominal Lymphatic Tumors in Women
Unknown status NCT00490789 - Trial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM Phase 2
Not yet recruiting NCT05087134 - Characterizing LAM With 11C-Choline PET/CT Early Phase 1
Completed NCT02009241 - Pulmonary Rehabilitation in Lymphangioleiomyomatosis N/A
Recruiting NCT05190627 - Effect of Loratadine in Lymphangioleiomyomatosis Phase 2
Completed NCT05323370 - Lymphangioleiomyomatosis, a Study on Cathepsin K
Completed NCT02859194 - The Effect of Lt to Rt Shunt Using Veno-veno-arterial Extracorporeal Membrane Oxygenation (ECMO) on Coronary Oxygenation in Lung Transplantation Patients N/A
Completed NCT03253913 - Resveratrol and Sirolimus in Lymphangioleiomyomatosis Trial Phase 2
Recruiting NCT02432560 - Safety and Durability of Sirolimus for Treatment of LAM
Completed NCT02061397 - Safety of Simvastatin in LAM and TSC Phase 1/Phase 2
Active, not recruiting NCT01552434 - Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease Phase 1
Recruiting NCT04577937 - Sleep Patterns in Patients Affected by Lymphangioleiomiomatosis N/A
Completed NCT00005906 - Treatment With Octreotide in Patients With Lymphangioleiomyomatosis Phase 2
Recruiting NCT01799538 - Nebulized or Inhaled Albuterol for Lymphangioleiomyomatosis Phase 1/Phase 2
Completed NCT00989742 - Doxycycline In Lymphangioleiomyomatosis (LAM) Phase 4
Recruiting NCT06160310 - Tuberous Sclerosis Complex and Lymphangioleiomyomatosis Pregnancy Registry (TSC-LAM Registry)
Enrolling by invitation NCT05727852 - Breath Analysis and Arterial Stiffness in Patients With Respiratory Diseases
Completed NCT03131999 - LAM Pilot Study With Imatinib Mesylate Phase 1/Phase 2