Characterization of the Pathogenesis of Primary and Secondary Lymphatic Disorders
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Lymphangiomatosis
- Sponsor
- National Heart, Lung, and Blood Institute (NHLBI)
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- (a) define the natural history of lymphatic diseases, (b) characterize the clinical phenotypes, and (c) elucidate their pathogenesis at the physiological, cellular and molecular levels.
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
Background:
- Lymphatics are a type of vessel, similar to arteries and veins. Lymphatic disorders happen when these vessels don t work properly. Researchers want to look for a relationship between lymphatic disorders and variations of certain genes found in the lung, blood, and other places in the body.
Objective:
- To learn more about lymphatic disorders and evaluate how genetic factors affect lymphatic disorders.
Eligibility:
- People ages 2 90 who have a lymphatic disorder or relatives of people with lymphatic disorders.
- Healthy volunteers 18 and older.
Design:
- Participants may have 1 2 visits a year, or more as needed. The study is expected to last 5 years. Visits may last 1 5 days. Participants may have lab tests, medical history, and physical exam at each visit.
- Participants may have blood testing that includes genetics tests, and urine tests. They may have nose and throat cultures, saliva collection, and cheek swabs to collect samples.
- Participants may have a skin biopsy and have blood taken from an artery.
- Participants may have breathing tests and be studied while exercising.
- Participants may have an electrocardiogram. Electrodes will be placed on their chest, tracing heart rhythms. They may also have chest X-rays.
- Participants may have a bronchoscopy. A thin, flexible instrument will be passed through the nose or mouth, into the lung. A tissue sample will be taken.
- Participants who have lymphatic disease or have a relative with it may also have:
- CT scans. They will lie on a table and hold their breath while their chest is scanned.
- MRI. They will lie flat on a table that slides in and out of a scanner.
- ultrasound. A probe is rolled around outside the abdomen.
- removal of fluid around the lungs, chest, and abdomen.
Detailed Description
Disorders of lymphatic function are associated with multiple presentations, the most common of which is lymphedema, a chronic swelling of the extremities, due to impaired lymphatic drainage. It can cause disability and a predisposition to infection and chronic ulceration. Other lymphatic disorders present with visceral manifestations such as regional or systemic lymphangiomatosis, pulmonary and intestinal lymphangiectasia, protein-losing enteropathy, chylous ascites, and chylothorax. Abnormalities of smooth muscle cell proliferation are associated with lymphangiomatosis. Proliferation of a neoplastic cell, the LAM cell, which exhibits a smooth muscle cell phenotype, is associated with lymphangioleiomyomatosis. Currently, treatment for many of these disorders is symptomatic and the prognosis is variable. The molecular mechanisms of lymphatic vasculogenesis are incompletely understood, but critical genes have been described, and mutations in these genes may lead to developmental abnormalities. There may be a genetic predisposition to lymphatic disorders, with a role for modifier genes in disease progression. The purpose of this study is to (a) define the natural history of lymphatic diseases, (b) characterize the clinical phenotypes, and (c) elucidate their pathogenesis at the physiological, cellular and molecular levels. This protocol is part of a Trans-Institute basic, translational and clinical initiative in lymphatic disorders and will include participation of principal investigators across the NIH, as well as extramural investigators.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
(a) define the natural history of lymphatic diseases, (b) characterize the clinical phenotypes, and (c) elucidate their pathogenesis at the physiological, cellular and molecular levels.
Time Frame: ongoing
To define the clinical phenotype of the lymphatic disorder.To define the molecular basis of the lymphatic disorders.This knowledge will help in improving our understanding of lymphatic proliferation in normal conditions as well as in disease.
Secondary Outcomes
- To assess the contribution of proteins and other genes to the clinical phenotype.(Undefined)