Universal Familial Hypercholesterolemia Screening in Children

NCT04507984 | Completed

• 1 other identifier: FHUniScreenPeds
• Study Type: observational
• Target: 17,000
• Locations: 2 countries
• Sites: 2

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).

Conditions

Familial Hypercholesterolemia; Polygenic Hypercholesterolaemia

Keywords

familial hypercholesterolemia; FH; screening; universal; cascade; pediatric

Outcome Measures

Primary Outcomes (1)

• Efficacy of universal familial hypercholesterolemia screening

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

  36 months

Secondary Outcomes (4)

• Genotype-phenotype correlations in children with familial hypercholesterolemia

  36 months

• Prevalences of heterozygous and homozygous familial hypercholesterolemia

  36 months

• Cost-effectiveness analysis of universal screening for familial hypercholesterolemia

  36 months

• Comparison of universal and pilot familial hypercholesterolemia screening

  36 months

Study Arms (4)

Children with hypercholesterolemia (Slovenia)

Children (aged 5 years) with total cholesterol measurement at primary care pediatricians at the programed visit prior to school entry.

Diagnostic Test: Lipid levels measurement

Children with hypercholesterolemia (Lower Saxony, Germany)

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.

Diagnostic Test: Lipid levels measurement

Children referred for FH genetic analysis (Slovenia and LS)

Children referred for familial hypercholesterolemia genetic analysis to the tertiary center, according to the screening algorithm.

Diagnostic Test: Genetic analysis; Diagnostic Test: Lipid levels measurement

Parents and siblings of children with confirmed FH (Slovenia)

Parents or siblings of index cases with completed familial hypercholesterolemia genetic analysis, according to the screening algorithm.

Diagnostic Test: Genetic analysis; Diagnostic Test: Lipid levels measurement

Interventions

Genetic analysis DIAGNOSTIC_TEST

After obtaining written consent from patients, DNA is isolated, and genetic analysis of the know familial hypercholesterolemia disease-causing genes (LDLR, APOB, PCSK9) is performed.

Children referred for FH genetic analysis (Slovenia and LS); Parents and siblings of children with confirmed FH (Slovenia)

Lipid levels measurement DIAGNOSTIC_TEST

Measurements of lipid levels (total cholesterol, LDL-cholesterol, HDL-cholesterol, TG) using standard methods.

Children referred for FH genetic analysis (Slovenia and LS); Children with hypercholesterolemia (Lower Saxony, Germany); Children with hypercholesterolemia (Slovenia); Parents and siblings of children with confirmed FH (Slovenia)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Slovenian cohort: A three-step approach of universal hypercholesterolemia screening is implemented: (1) total cholesterol (TC) measurement in all children at their primary care pediatricians at the programed visit prior to school entry; (2) if above the cut-off, re-testing and/or referral to the lipid clinic, where fasting LDL-cholesterol (LDL-C) measurement is performed; if again above the cut-off, it is followed by FH genetic testing; (3) if FH confirmed, screening of parent with higher TC/LDL-C level. Lower Saxony cohort: (1) LDL-C measurement was offered to all children between 2-6 years during the compulsory routine check-ups and at any voluntary visits to the pediatrician's office; (2) if twice above the cut-off, referral to the lipid clinic, followed by FH genetic testing.

You may qualify if:

• 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).

You may not qualify if:

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

Sponsors & Collaborators

• University of Ljubljana, Faculty of Medicine: lead
• University Medical Centre Ljubljana: collaborator
• Kinderkrankenhaus auf der Bult: collaborator

Study Sites (2)

Children's Hospital AUF DER BULT

Hanover, 30173, Germany

Location

UMC - University Children's Hospital Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (6)

• Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Boren J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjaerg-Hansen A; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013 Dec;34(45):3478-90a. doi: 10.1093/eurheartj/eht273. Epub 2013 Aug 15.

  PMID: 23956253 BACKGROUND

• Wiegman A, Gidding SS, Watts GF, Chapman MJ, Ginsberg HN, Cuchel M, Ose L, Averna M, Boileau C, Boren J, Bruckert E, Catapano AL, Defesche JC, Descamps OS, Hegele RA, Hovingh GK, Humphries SE, Kovanen PT, Kuivenhoven JA, Masana L, Nordestgaard BG, Pajukanta P, Parhofer KG, Raal FJ, Ray KK, Santos RD, Stalenhoef AF, Steinhagen-Thiessen E, Stroes ES, Taskinen MR, Tybjaerg-Hansen A, Wiklund O; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015 Sep 21;36(36):2425-37. doi: 10.1093/eurheartj/ehv157. Epub 2015 May 25.

  PMID: 26009596 BACKGROUND

• Representatives of the Global Familial Hypercholesterolemia Community; Wilemon KA, Patel J, Aguilar-Salinas C, Ahmed CD, Alkhnifsawi M, Almahmeed W, Alonso R, Al-Rasadi K, Badimon L, Bernal LM, Bogsrud MP, Braun LT, Brunham L, Catapano AL, Cillikova K, Corral P, Cuevas R, Defesche JC, Descamps OS, de Ferranti S, Eisele JL, Elikir G, Folco E, Freiberger T, Fuggetta F, Gaspar IM, Gesztes AG, Groselj U, Hamilton-Craig I, Hanauer-Mader G, Harada-Shiba M, Hastings G, Hovingh GK, Izar MC, Jamison A, Karlsson GN, Kayikcioglu M, Koob S, Koseki M, Lane S, Lima-Martinez MM, Lopez G, Martinez TL, Marais D, Marion L, Mata P, Maurina I, Maxwell D, Mehta R, Mensah GA, Miserez AR, Neely D, Nicholls SJ, Nohara A, Nordestgaard BG, Ose L, Pallidis A, Pang J, Payne J, Peterson AL, Popescu MP, Puri R, Ray KK, Reda A, Sampietro T, Santos RD, Schalkers I, Schreier L, Shapiro MD, Sijbrands E, Soffer D, Stefanutti C, Stoll M, Sy RG, Tamayo ML, Tilney MK, Tokgozoglu L, Tomlinson B, Vallejo-Vaz AJ, Vazquez-Cardenas A, de Luca PV, Wald DS, Watts GF, Wenger NK, Wolf M, Wood D, Zegerius A, Gaziano TA, Gidding SS. Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action. JAMA Cardiol. 2020 Feb 1;5(2):217-229. doi: 10.1001/jamacardio.2019.5173.

  PMID: 31895433 BACKGROUND

• Klancar G, Groselj U, Kovac J, Bratanic N, Bratina N, Trebusak Podkrajsek K, Battelino T. Universal Screening for Familial Hypercholesterolemia in Children. J Am Coll Cardiol. 2015 Sep 15;66(11):1250-1257. doi: 10.1016/j.jacc.2015.07.017.

  PMID: 26361156 BACKGROUND

• Groselj U, Kovac J, Sustar U, Mlinaric M, Fras Z, Podkrajsek KT, Battelino T. Universal screening for familial hypercholesterolemia in children: The Slovenian model and literature review. Atherosclerosis. 2018 Oct;277:383-391. doi: 10.1016/j.atherosclerosis.2018.06.858.

  PMID: 30270075 BACKGROUND

• Kordonouri O, Lange K, Boettcher I, Christoph J, Marquardt E, Tombois C, Galuschka L, Stiller D, Mueller I, Roloff F, Aschemeier B, Danne T. New approach for detection of LDL-hypercholesterolemia in the pediatric population: The Fr1dolin-Trial in Lower Saxony, Germany. Atherosclerosis. 2019 Jan;280:85-91. doi: 10.1016/j.atherosclerosis.2018.11.011. Epub 2018 Nov 17.

  PMID: 30496984 BACKGROUND

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Interventions

Genetic Testing

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Urh Groselj, MD, PhD

  University of Ljubljana, Faculty of Medicine

  PRINCIPAL INVESTIGATOR

• Olga Kordonouri, MD, PhD

  Kinderkrankenhaus auf der Bult

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2020
• First Posted: August 11, 2020
• Study Start: January 1, 2019
• Primary Completion: August 1, 2020
• Study Completion: December 31, 2021
• Last Updated: May 18, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); SL (1)