Characterization of the Pathogenesis of Lymphangioleiomyomatosis (LAM)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,000
- 试验地点
- 1
- 主要终点
- Define the clinical course of the disease LAM andelucidate the pathogenesis of LAM at cellular and molecular levels
研究概览
简要总结
Pulmonary lymphangioleiomyomatosis (LAM) is a destructive lung disease typically affecting women of childbearing age. Currently, there is no effective therapy for the disease and the prognosis is poor.
This study is designed to determine the disease processes involved at the level of cells and molecules, in order to develop more effective therapy.
Researchers intend to identify the proteins and genes that contribute to the process of lung destruction in affected individuals.
详细描述
Individuals with pulmonary lymphangioleiomyomatosis develop severe destructive lung disease. Many of them are females of childbearing age. Currently, sirolimus is a proven therapy, but it is not effective in all patients and the prognosis is variable. This study is designed to (a) define the clinical course of the disease and (b) elucidate the pathogenesis of the disease at the cellular and molecular levels, in order to develop more effective therapies. To accomplish this, we intend to identify the proteins and genes that contribute to the process of lung destruction in affected individuals.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 16 Years 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •General admission criteria for patients include one or both of the following:
- •Findings on lung biopsy diagnostic of LAM;
- •Findings on chest x-ray and/or chest computed axial tomography consistent with LAM.
- •Patients with TSC and pulmonary LAM will be included in the study.
- •Normal non-smokers in the control group are defined as individuals who have not smoked for greater than or equal to 1 year and have no systemic or pulmonary disease.
- •Normal smokers defined as individuals with no systemic or pulmonary disease, who have smoked for greater than or equal to 1 year and have normal chest x-ray and normal pulmonary function tests may be included if needed as controls for a similar population of patients with LAM.
- •Pregnant and or nursing women including pregnant minors may be included in accordance with Federal Regulations at Subpart B of 45 CFR
- •Subjects who are pregnant and or nursing will be excluded from procedures during their pregnancy that are greater than minimal risk, until they are no longer pregnant and/or nursing. A minor participant with a positive pregnancy test result will be informed promptly. The result will be discussed in a sensitive and developmentally appropriate manner with the minor, including explanation of the result, assessment of safety, and referral for appropriate follow-up care. The participant will be informed of the limits of confidentiality. The study team will encourage involvement of a parent or legal guardian when appropriate and safe. If there is concern for abuse, coercion, exploitation, or danger, the study team will follow applicable mandatory reporting laws and institutional policies, including notification of appropriate authorities and/or a parent or guardian when required to protect the participant or as otherwise required.
- •Procedures that will not be completed while the subject is pregnant and/or nursing include: Arterial Blood Gases (ABG), HIV testing, treadmill test, lung biopsy, thoracentesis, bronchoscopy, and measurements with imaging modalities requiring contrast or with radiation exposure such as Chest x-ray, CT scan, MRI with or without contrast, lung scan, bone densitometry (DEXA). Allowing subjects to be included in the study may glean important information about individuals with uncommon pulmonary disease during and post pregnancy.
- •Rationale for inclusion of children (16 to < 18 years of age):
- •LAM is a rare progressive disease that can manifest during adolescence, particularly in individuals with TSCassociated disease. Participation is expected to provide clinically meaningful evaluation and/or contribute important information about the natural history and presentation of LAM in younger patients. At age 16, the participant is generally capable of providing meaningful consent, understanding study procedures, and participating in discussions about risks, burdens, and potential benefits.
排除标准
- •Exclusion criteria for patients include:
- •Age less than
- •Advanced stage of a pulmonary or a systemic illness in which the risk of the study is judged to be significant even in the absence of a clear contraindication to the procedures.
- •Exclusion criteria for patients for the formal exercise study and the stress echocardiogram include patients on continuous oxygen. Patients may perform an exercise test that will assess the patient's exercise capacity with activities of daily living.
研究组 & 干预措施
LAM
Patients with tissue diagnosis of LAM may be admitted for evaluation every six months, or as deemed necessary for research
干预措施: Toshibia Aquilion One CT (Device)
结局指标
主要结局
Define the clinical course of the disease LAM andelucidate the pathogenesis of LAM at cellular and molecular levels
时间窗: on going
To define the molecular basis of the remarkable proliferation of immature appearing smooth muscle cells, which is the cause of many of the clinical manifestations, and perhaps thereby to improve our understanding of the mechanism of smooth muscle cell proliferation in other diseases, e.g., interstitial lung diseases, asthma, atherosclerosis, hypertension, and post-angioplastic coronary restenosis. To assess the contribution of proteins and genetic factors to cyst formation, airway obstruction, and clinical course. To evaluate the role of TSC genes in the pathogenesis of LAM.
次要结局
未报告次要终点