Universal Familial Hypercholesterolemia Screening in Children

Completed

• Conditions: Familial Hypercholesterolemia; Polygenic Hypercholesterolaemia
• Interventions: Diagnostic Test: Genetic analysis; Diagnostic Test: Lipid levels measurement

• Registration Number: NCT04507984
• Lead Sponsor: University of Ljubljana, Faculty of Medicine

Brief Summary

30 million individuals globally with undiagnosed familial hypercholesterolemia (FH) are at a substantial cardiovascular disease (CVD) risk, which could be normalized by early diagnosis and treatment. Effective screening strategies are urgently needed, but the data on universal FH screening (uFHs) is scarce.

The investigators aim to assess the overall performance of the uFHs program in Slovenia and to compare the common elements to the pilot uFHs program in Lower Saxony (LS; Germany).

Detailed Description

The study will include pediatric patients (or their siblings and parents in Slovenian cohort) undergoing the universal hypercholesterolemia screening; those with elevated cholesterol at universal cholesterol screening at primary care level are referred to the lipidology specialist at the UMC Ljubljana (Slovenia) or Kinderkrankenhaus auf der Bult (Lower Saxony, Germany). For those with elevated cholesterol levels, the familial hypercholesterolemia genetic diagnostics is done centrally in UMC Ljubljana.

Only those will be included from whom a signed informed consent by themselves or by their parents/guardians will be obtained prior to the genetic diagnosis of familial hypercholesterolemia.

Study Timeline

• Study Start: 2019-01-01
• Study First Submitted: 2020-07-28
• Primary Completion: 2020-08-01
• Study First Submitted QC: 2020-08-07
• Study First Posted: 2020-08-11
• Study Completion: 2021-12-31
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-17
• Last Update Posted: 2023-05-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17000

Inclusion Criteria

• Elevated total cholesterol (cohort 1) or LDL-cholesterol (cohort 2) at universal screening program in children.
• Completed FH genetic analysis (cohort 3).
• Parent or sibling of child with confirmed familial hypercholesterolemia (cohort 4).

Exclusion Criteria

• Children with hypercholesterolemia not referred through the screening program.
• FH genetic analysis not completed.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Children referred for FH genetic analysis (Slovenia and LS)	Lipid levels measurement	Children referred for familial hypercholesterolemia genetic analysis to the tertiary center, according to the screening algorithm.
Parents and siblings of children with confirmed FH (Slovenia)	Genetic analysis	Parents or siblings of index cases with completed familial hypercholesterolemia genetic analysis, according to the screening algorithm.
Parents and siblings of children with confirmed FH (Slovenia)	Lipid levels measurement	Parents or siblings of index cases with completed familial hypercholesterolemia genetic analysis, according to the screening algorithm.
Children with hypercholesterolemia (Slovenia)	Lipid levels measurement	Children (aged 5 years) with total cholesterol measurement at primary care pediatricians at the programed visit prior to school entry.
Children with hypercholesterolemia (Lower Saxony, Germany)	Lipid levels measurement	Children (aged 2-6 years) with LDL-cholesterol measurement during the compulsory routine check-ups and at any voluntary visits to the primary care pediatricians.
Children referred for FH genetic analysis (Slovenia and LS)	Genetic analysis	Children referred for familial hypercholesterolemia genetic analysis to the tertiary center, according to the screening algorithm.

Primary Outcome Measures

Name	Time	Method
Efficacy of universal familial hypercholesterolemia screening	36 months	The investigators aim to assess the overall performance (number of cases per 1000/screened; rate of implementation) of the universal screening for familial hypercholesterolemia.

Secondary Outcome Measures

Name	Time	Method
Genotype-phenotype correlations in children with familial hypercholesterolemia	36 months	The investigators will assess the phenotypic characteristics in relation to genotypes; specificity and sensitivity of genetic analyses will be determined.
Comparison of universal and pilot familial hypercholesterolemia screening	36 months	The investigators aim to compare the common elements of the pilot universal hypercholesterolemia program in Lower Saxony (LS; Germany) to the Slovenian national universal familial hypercholesterolemia screening.
Prevalences of heterozygous and homozygous familial hypercholesterolemia	36 months	Number of genetically confirmed cases are compared to the number of live-born children in same period.
Cost-effectiveness analysis of universal screening for familial hypercholesterolemia	36 months	The costs per new genetically confirmed case are estimated considering the costs for all the three steps of the screening algorithm.

Trial Locations

Locations (2)

Children's Hospital AUF DER BULT; 🇩🇪 Hannover, Germany

UMC - University Children's Hospital Ljubljana; 🇸🇮 Ljubljana, Slovenia