Clinical Trial: Clinical and Basic Investigations Into Erdheim Chester Disease
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational
Official Title: Clinical and Basic Investigations Into Erdheim-Chester Disease
Brief Summary:
Background:
- Erdheim Chester Disease (ECD) is a very rare disease in which abnormal white blood cells start growing and affect the bones, kidneys, skin, and brain. ECD can cause severe lung disease, kidney failure, heart disease, and other complications that lead to death. Because ECD is a rare disease, found mostly in men over 40 years of age, there is no standard treatment for it. More information is needed to find out what genes can cause ECD and how best to treat it.
Objectives:
- To collect study samples and medical information on people with Erdheim Chester Disease.
Eligibility:
- Individuals 2 to 80 year of age who have been diagnosed with Erdheim Chester Disease.
Design:
- Participants will be screened with a physical exam and medical history.
- Participants will have a study visit to provide samples for study, including blood, urine, and skin tissue samples. Participants will also have lung, heart, and muscle function tests; imaging studies of the brain, chest, and whole body; a treadmill running stress test; an eye exam; and other tests as needed by the study doctors.
- Participants will be asked to return for a similar set of tests every 2 years, and to remain in contact for possible treatment options.
Detailed Summary: Erdheim-Chester Diseases (ECD) is a very rare non-Langerhans cell histiocytosis of unknown origin and pathogenesis. It has been reported mainly in adult males over the age of 40 years, although cases have been reported in females as well. Children are rarely affected by this condition. Mutation of the BRAF gene has been recently identified in 50% of Erdheim Chester lesions in a French cohort18; family studies have not been performed due to the rarity and sporadic nature of the disease. The clinical characteristics of ECD range from asymptomatic to multisystemic involvement; longitudinal progression and natural history have not been well documented. ECD commonly affects the bones, kidneys, retroperitoneal space, skin and brain. After diagnosis, the disease progresses rapidly, causing fatal outcomes due to severe lung disease, chronic renal failure, cardiomyopathy and other complications. The diagnosis of ECD relies upon imaging studies and specific pathologic findings in biopsies of affected organs, i.e., fibrosis and infiltration of the affected tissues with foamy histiocytes, lymphocytes, and plasma cells. Immunohistochemistry reveals cells positive for CD68, CD 163 and negative for CD1a and S-100; although a 20% positivity has been reported for the S-100 marker. There is no standard treatment for ECD, although chemotherapy with cladribine, radiation, stem cell transplantation, alpha-interferon, anakinra, imatinib, steroids and sirolimus have been proposed. Symptomatic improvement has been reported with some of these therapies, but death within a few years after diagnosis remains the expected outcome. For patients where the BRAF V600E mutation has been detected, the use of BRAF Inhibitors such as vemurafenib is currently under study. We are currently studying the use of Dabrafnib and Trametinib in patients with the BRAF V600E mutation. In this protocol, we will clinically evaluate ECD patients, obtain cells, plasma, and urine, search for genes that can be responsib
Sponsor: National Human Genome Research Institute (NHGRI)
Current Primary Outcome:
Original Primary Outcome:
Current Secondary Outcome:
Original Secondary Outcome:
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: August 13, 2011
Date Started: July 29, 2011
Date Completion:
Last Updated: April 20, 2017
Last Verified: April 3, 2017
