Extreme Lipid Phenotypes in Autosomal Dominant Hypercholesterolemia: The ELePHANT Study

Completed

Conditions: Autosomal Dominant Hypercholesterolaemia
Inherited Hypercholesterolaemia
10083624

Registration Number: NL-OMON40882

Lead Sponsor: Academisch Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

I) Individuals with molecular defined homozygous ADH (two molecular defects in two different alleles in the ADH causing genes (LDLR, APOB or PCSK9)) without the clinical phenotype for homozygous ADH (LDL-C < 13 mmol/L). OR
II) Patients heterozygous for ADH causing mutations AND a phenotype compatible with clinical homozygous ADH (LDL-C levels > 13 mmol/L without lipid lowering therapy or LDL-C levels > 7.8 mmol/L while receiving maximal dose of a statin and ezetimibe) (according to the clinical criteria for homozygous ADH).

Exclusion Criteria

Indication of another clinical condition that (in the opinion of the investigator) might explain the extreme ADH phenotype
I) Thyroid dysfunction
II) Renal insufficiency
III) Cholestasis
IV) Alcohol use
V) Use of medication known to impact lipid metabolism (including but not limited to psychopharmacologic therapeutics, protease inhibitors, beta blockers, thiazide diuretics).

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1) Identification of novel (epi) genetic causes of extreme ADH phenotypes.<br /><br>2) Carotid IMT measurements:<br /><br>- The mean difference in age and gender adjusted cIMT between the two extreme<br /><br>ADH populations.<br /><br>- The mean difference in age and gender adjusted cIMT between the separate ADH<br /><br>populations and their first and second degree relatives. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Mean difference in age and gender adjusted cIMT between molecularly defined<br /><br>homozygous and molecularly defined heterozygous ADH patients matched for age,<br /><br>gender and plasma LDL-C levels. To reach this endpoint, homozygous ADH patients<br /><br>in our cohort will be matched with heterozygote ADH patients in whom a cIMT<br /><br>measurement was previously performed (METC 07/138#). </p><br>