Familial Hypobetalipoproteinaemia - Heterozygous Form Clinical Trial
Official title:
Characterization of Two Novel Truncating Mutations in the Apob Gene Leading to Hypobetalipoproteinemia: A Pilot Study
The pilot study has the target to evaluate the outcomes of two novel mutations in the gene of
Apolipoprotein B (ApoB). ApoB is the main part of the low-density lipoprotein (LDL). LDL is
the main transporter of cholesterol from the liver to the periphery. The two novel mutations
lead to a heavily truncated Apolipoprotein B. Therefore the patients show severely decreased
ApoB and LDL-Cholesterol levels. The acquired disease is known as "Familial
Hypobetalipoproteinemia". Beside the protection from cardiovascular disease due to decreased
LDL-Cholesterol, patients tend to show elevated serum aminotransferases, fatty liver and
occasional cases of cirrhosis and carcinoma.
To elucidate the differences in lipoprotein assembly the investigators aim to characterize
the changes due to the mutations in the patients. Family members not carrying the mutations
are the control group. The assessment includes lipoprotein fractionation, MRI scans of the
liver and a thorough assessment of medical history of all patients to look for potential side
effects of the mutation.
The only intervention needed for the study is to draw blood samples of every participant. The
necessary positive vote from the ethics committee of the Medical University of Innsbruck is
given.
Status | Recruiting |
Enrollment | 16 |
Est. completion date | January 2022 |
Est. primary completion date | January 2021 |
Accepts healthy volunteers | |
Gender | All |
Age group | 18 Years to 85 Years |
Eligibility |
Inclusion Criteria: - Full legal age - Written Informed Consent - Diagnosed hypobetalipoproteinemia - Exception of it are the controls - Controls have to be family members - Exclusion of a truncating mutation in the ApoB gene Exclusion Criteria: - No diagnosed hypobetalipoproteinemia - No truncating mutation in the Apo B gene - Exception of it ar the controls |
Country | Name | City | State |
---|---|---|---|
Austria | Medical University Innsbruck | Innsbruck | Tyrol |
Lead Sponsor | Collaborator |
---|---|
Medical University Innsbruck |
Austria,
Di Costanzo A, Di Leo E, Noto D, Cefalù AB, Minicocci I, Polito L, D'Erasmo L, Cantisani V, Spina R, Tarugi P, Averna M, Arca M. Clinical and biochemical characteristics of individuals with low cholesterol syndromes: A comparison between familial hypobetalipoproteinemia and familial combined hypolipidemia. J Clin Lipidol. 2017 Sep - Oct;11(5):1234-1242. doi: 10.1016/j.jacl.2017.06.013. Epub 2017 Jun 24. — View Citation
Hooper AJ, Heeks L, Robertson K, Champain D, Hua J, Song S, Parhofer KG, Barrett PH, van Bockxmeer FM, Burnett JR. Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia. J Clin Endocrinol Metab. 2015 Nov;100(11):E1484-90. doi: 10.1210/jc.2015-2731. Epub 2015 Aug 31. — View Citation
Schonfeld G. Familial hypobetalipoproteinemia: a review. J Lipid Res. 2003 May;44(5):878-83. Epub 2003 Mar 16. Review. — View Citation
Welty FK. Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol. 2014 Jun;25(3):161-8. doi: 10.1097/MOL.0000000000000072. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Difference in lipoprotein profiles | Lipoprotein profiles are measured via Fast Protein Liquid Chromatography in both groups and compared. | 6 months | |
Primary | Differences in amounts of liver fat | Liver fat is non-invasive quantified by MRI scan | 12 months | |
Primary | Differences in HDL-efflux | Compare the results between groups of HDL-efflux assays | 6 months |