Cholesteryl Ester Storage Disease Clinical Trial
— LAL-DOfficial title:
The Frequency of Cholesteryl Ester Storage Disease in Children With Unexplained Transaminase Elevation and Chronic Liver Disease
| Verified date | November 2017 |
| Source | Ankara University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
Cholesteryl Ester Storage Disease (CESD) is an autosomal recessive lysosomal storage disorder
(LSD) caused by mutations in the lysosomal acid lipase gene (LIPA) that markedly reduce
lysosomal acid lipase (LAL) activity, leading to the accumulation of lipids, predominately
cholesteryl esters and triglycerides, in various tissues and cell types. In the liver,
accumulation of lipids leads to diffuse microvesicular steatosis, which progresses to
fibrosis and ultimately, to micronodular cirrhosis. Patients typically present with
hepatomegaly, liver dysfunction, hepatic failure and type II hyperlipidemia. Although
hepatosteatosis is a typical finding, the liver biopsy diagnosis may be misclassified as
non-alcoholic fatty liver disease, non-alcoholic steatohepatitis or cryptogenic liver
disease. Biopsy and radiological findings are not considered diagnostic, but help to
suspicion of CESD. The definitive diagnosis is based on deficient LAL activity and/or LIPA
gene mutations.
CESD is pan-ethnic, however, the disease incidence is unknown. The estimated incidence of the
disease indicates that CESD should be largely underdiagnosed especially in European patients.
Elevation of serum transaminases, and hepatomegaly are early indications of liver impairment.
Therefore, CESD should be considered as a differential diagnosis in liver disease of unknown
origin.
To data, there is no study which evaluated the frequency of CESD in children with unexplained
transaminase elevation and/or organomegaly and/or chronic liver disease. The aim of this
prospective, multicenter and cross-sectional study is to investigate frequency of CESD in
children with unexplained transaminase elevation and/or and/or chronic liver disease and to
identify demographic and clinical features of CESD.
| Status | Completed |
| Enrollment | 810 |
| Est. completion date | March 1, 2017 |
| Est. primary completion date | January 31, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 3 Months to 18 Years |
| Eligibility |
Inclusion Criteria: 1. A male or female of 3 months to 18 years of age at the time of enrolment 2. Patients who have unexplained transaminase elevation (serum ALT levels > 1.5 times the upper limit of normal) for more than 3 months 3. Patients who have unexplained hepatomegaly or hepatosplenomegaly 4. Patients who have obesity- unrelated hepatosteatosis 5. Patients who have biopsy-proven cryptogenic fibrosis and cirrhosis 6. Patients with liver transplantation for cryptogenic cirrhosis Exclusion Criteria: 1. A male or female < 3 months or > 18 years old 2. Patients with obesity -related hepatosteatosis 3. Patients with drug-induced hepatosteatosis ( such as aspirin, methotrexate, amiodarone, glucocorticoid, tamoxifen, 5-fluorouracil, valproate, nucleoid revers transcriptase inhibitors) 4. Patients with organomegaly or transaminase elevation due to infectious causes (EBV, Brucella, cytomegalovirus, salmonella, malaria, leishmania etc), hæmato-oncological disease (hemolytic anemia, leukemia,lymphoma, malign or benign liver neoplasms), connective tissue disorders (SLE, RA), cardiac and vascular causes (heart failure, pericarditis, Budd-Chiari syndrome, portal vein thrombosis) and obesity. 5. Patient with definitive diagnosed chronic liver disease such as chronic viral hepatitis (B, C hepatitis), autoimmune hepatitis, alpha-1 antitrypsin deficiency, Wilson disease, metabolic disorders. |
| Country | Name | City | State |
|---|---|---|---|
| Turkey | Ankara University School of Medicine | Ankara |
| Lead Sponsor | Collaborator |
|---|---|
| Ankara University | Alexion Pharmaceuticals |
Turkey,
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* Note: There are 14 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Frequency of Cholesteryl Ester Storage Disease in children who have unexplained transaminase elevation for more than 3 months and/or organomegaly and/or hepatosteatosis unrelated to obesity and/or cryptogenic fibrosis and cirrhosis | First day | ||
| Secondary | Identify demographic and clinical features of Cholesteryl Ester Storage Disease | First day |