Clinical trial NCT03963037: Characterization of Two Novel Mutations in the Apob Gene
Official title: Characterization of Two Novel Truncating Mutations in the Apob Gene Leading to Hypobetalipoproteinemia: A Pilot Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Familial Hypobetalipoproteinaemia - Heterozygous Form
Low-LDL-syndrome
Keywords: Apolipoprotein B
Cholesterol
Lipoprotein
Metabolism
Steatosis
Cirrhosis
Hepatocellular Carcinoma
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
First posted: 2019-05-24
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The participants descend from two families. Each family carries a novel truncating mutation in the ApoB gene. The family members decided to participate in our pilotstudy to elucidate the changes caused by the mutations. Familial hypobetalipoproteinemia is a codominant disorder, so family members not carrying the mutations serve as control group.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Difference in lipoprotein profiles
timeFrame: 6 months
measure: Differences in amounts of liver fat
timeFrame: 12 months
measure: Differences in HDL-efflux
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
state: Tyrol
Study officials:
affiliation: Department of Internal Medicine I, Medical University of Innsbruck, Austria
name: Christoph Ebenbichler, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Welty FK. Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol. 2014 Jun;25(3):161-8. doi: 10.1097/MOL.0000000000000072.
citation: Di Costanzo A, Di Leo E, Noto D, Cefalu 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.
citation: Schonfeld G. Familial hypobetalipoproteinemia: a review. J Lipid Res. 2003 May;44(5):878-83. doi: 10.1194/jlr.R300002-JLR200. Epub 2003 Mar 16.
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.