Universal Familial Hypercholesterolemia Screening in Children

Familial Hypercholesterolemia Clinical Trial

Official title:

Universal Screening for Familial Hypercholesterolemia in Children - a Practical Approach

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04507984
• Other study ID #: FHUniScreenPeds
• Status: Completed
• Start date: January 1, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: May 2023
• Source: University of Ljubljana, Faculty of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17000
• Est. completion date: December 31, 2021
• Est. primary completion date: August 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II
• Polygenic Hypercholesterolaemia

Intervention

Diagnostic Test:
• Genetic analysis
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.
• Lipid levels measurement
Measurements of lipid levels (total cholesterol, LDL-cholesterol, HDL-cholesterol, TG) using standard methods.

Locations

Country	Name	City	State
Germany	Children's Hospital AUF DER BULT	Hannover
Slovenia	UMC - University Children's Hospital Ljubljana	Ljubljana

Sponsors (3)

Lead Sponsor	Collaborator
University of Ljubljana, Faculty of Medicine	Kinderkrankenhaus auf der Bult, University Medical Centre Ljubljana

Countries where clinical trial is conducted

Germany,  Slovenia, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Eur Heart J. 2020 Dec 14;41(47):4517. — View Citation

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. Erratum In: JAMA Cardiol. 2020 May 1;5(5):613. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Genotype-phenotype correlations in children with familial hypercholesterolemia	The investigators will assess the phenotypic characteristics in relation to genotypes; specificity and sensitivity of genetic analyses will be determined.	36 months
Secondary	Prevalences of heterozygous and homozygous familial hypercholesterolemia	Number of genetically confirmed cases are compared to the number of live-born children in same period.	36 months
Secondary	Cost-effectiveness analysis of universal screening for familial hypercholesterolemia	The costs per new genetically confirmed case are estimated considering the costs for all the three steps of the screening algorithm.	36 months
Secondary	Comparison of universal and pilot familial hypercholesterolemia screening	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.	36 months