National Lysosomal Acid Lipase Deficiency Study

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

810 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-01-31

Study Completion Date

2017-03-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Patients of 3 months to 18 years of age at the time of enrolment who have unexplained transaminase elevation (serum alanine aminotransferase (ALT) levels \> 1.5 times the upper limit of normal) for more than 3 months and/or unexplained hepatomegaly or hepatosplenomegaly and/or obesity- unrelated hepatosteatosis and/or biopsy-proven cryptogenic fibrosis and cirrhosis and/or liver transplantation for cryptogenic cirrhosis will be included.

Potential participants will be invited for LAL enzyme analysis. Written informed consent will be obtained from the parents or guardians of the participants at the time of enrolment. Prospective and retrospective data will be collected. Complete family and medical history, physical examination and previously existing laboratory findings will be recorded on standard case reports form and up to 0.25 ml of blood will be drawn for LAL enzyme analysis. The blood obtained from participants will be spotted on filter paper, and dried blood spot sample (DBS) will be prepared. Finally, the dried blood spot sample will be sent to reference laboratory (NHS Greater Glasgow and Clyde, England) for LAL enzyme measurement within 1 week.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cholesteryl Ester Storage Disease

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Cholesteryl Ester Storage Disease Children Liver disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

Minimum Eligible Age

3 Months

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Zarife Kuloglu

Professor (M.D.)

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Zarife Kuloglu, M.D

Role: STUDY_DIRECTOR

Ankara University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Ankara University School of Medicine

Ankara, , Turkey (Türkiye)

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Turkey (Türkiye)

Review additional registry numbers or institutional identifiers associated with this trial.

LALD-TR

Identifier Type: -

Identifier Source: org_study_id

National Lysosomal Acid Lipase Deficiency Study

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Alexion Pharmaceuticals, Inc.

Ankara University

Responsible Party

Zarife Kuloglu

Principal Investigators

Zarife Kuloglu, M.D

Locations

Ankara University School of Medicine

Countries

References

Reynolds T. Cholesteryl ester storage disease: a rare and possibly treatable cause of premature vascular disease and cirrhosis. J Clin Pathol. 2013 Nov;66(11):918-23. doi: 10.1136/jclinpath-2012-201302. Epub 2013 Sep 2.

Hulkova H, Elleder M. Distinctive histopathological features that support a diagnosis of cholesterol ester storage disease in liver biopsy specimens. Histopathology. 2012 Jun;60(7):1107-13. doi: 10.1111/j.1365-2559.2011.04164.x.

Zhang B, Porto AF. Cholesteryl ester storage disease: protean presentations of lysosomal acid lipase deficiency. J Pediatr Gastroenterol Nutr. 2013 Jun;56(6):682-5. doi: 10.1097/MPG.0b013e31828b36ac.

Hamilton J, Jones I, Srivastava R, Galloway P. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chim Acta. 2012 Aug 16;413(15-16):1207-10. doi: 10.1016/j.cca.2012.03.019. Epub 2012 Mar 29.

Ambler GK, Hoare M, Brais R, Shaw A, Butler A, Flynn P, Deegan P, Griffiths WJ. Orthotopic liver transplantation in an adult with cholesterol ester storage disease. JIMD Rep. 2013;8:41-6. doi: 10.1007/8904_2012_155. Epub 2012 Jul 24.

Dalgic B, Sari S, Gunduz M, Ezgu F, Tumer L, Hasanoglu A, Akyol G. Cholesteryl ester storage disease in a young child presenting as isolated hepatomegaly treated with simvastatin. Turk J Pediatr. 2006 Apr-Jun;48(2):148-51.

Bernstein DL, Hulkova H, Bialer MG, Desnick RJ. Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol. 2013 Jun;58(6):1230-43. doi: 10.1016/j.jhep.2013.02.014. Epub 2013 Feb 26.

Fouchier SW, Defesche JC. Lysosomal acid lipase A and the hypercholesterolaemic phenotype. Curr Opin Lipidol. 2013 Aug;24(4):332-8. doi: 10.1097/MOL.0b013e328361f6c6.

Muntoni S, Wiebusch H, Jansen-Rust M, Rust S, Seedorf U, Schulte H, Berger K, Funke H, Assmann G. Prevalence of cholesteryl ester storage disease. Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1866-8. doi: 10.1161/ATVBAHA.107.146639. No abstract available.

Other Identifiers

LALD-TR