Characterization of Two Novel Mutations in the Apob Gene

NCT03963037 | Unknown

• 1 other identifier: 20190130-1943
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Familial Hypobetalipoproteinaemia - Heterozygous Form; Low-LDL-syndrome

Keywords

Apolipoprotein B; Cholesterol; Lipoprotein; Metabolism; Steatosis; Cirrhosis; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

• Difference in lipoprotein profiles

  Lipoprotein profiles are measured via Fast Protein Liquid Chromatography in both groups and compared.

  6 months

• Differences in amounts of liver fat

  Liver fat is non-invasive quantified by MRI scan

  12 months

• Differences in HDL-efflux

  Compare the results between groups of HDL-efflux assays

  6 months

Study Arms (2)

Patients

The family members of our two kindreds who carry the truncating mutation in the Apolipoprotein B gene.

Other: Blood draw

Controls

The family members of our two kindreds who are no carriers of the truncating mutation in the Apolipoprotein B gene.

Other: Blood draw

Interventions

Blood draw OTHER

Draw venous blood for baseline blood parameters and plasma samples for lipoprotein fractionation.

Controls; Patients

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Full legal age
• Written Informed Consent
• Diagnosed hypobetalipoproteinemia
• Exception of it are the controls
• Controls have to be family members

You may not qualify if:

• No diagnosed hypobetalipoproteinemia
• No truncating mutation in the Apo B gene
• Exception of it ar the controls

Sponsors & Collaborators

• Medical University Innsbruck: lead

Study Sites (1)

Medical University Innsbruck

Innsbruck, Tyrol, 6020, Austria

RECRUITING

Related Publications (4)

• Welty FK. Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol. 2014 Jun;25(3):161-8. doi: 10.1097/MOL.0000000000000072.

  PMID: 24751931 BACKGROUND

• 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.

  PMID: 28733173 BACKGROUND

• 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.

  PMID: 12639976 BACKGROUND

• 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.

  PMID: 26323024 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Whole blood.

MeSH Terms

Conditions

Fatty Liver; Fibrosis; Carcinoma, Hepatocellular

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Christoph Ebenbichler, MD, Prof.

  Department of Internal Medicine I, Medical University of Innsbruck, Austria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clemens Engler, MD

CONTACT

+43 512 504 83659; clemens.engler@i-med.ac.at

Christoph Ebenbichler, MD, Prof.

CONTACT

christoph.ebenbichler@i-med.ac.at

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: May 24, 2019
• Study Start: January 24, 2019
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2022
• Last Updated: February 20, 2020

Record last verified: 2020-02

Locations

AU (1)