Universal Familial Hypercholesterolemia Screening in Children

NCT ID: NCT04507984

Last Updated: 2023-05-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

17000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-01-01

Study Completion Date

2021-12-31

Brief Summary

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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

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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.

Conditions

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Familial Hypercholesterolemia Polygenic Hypercholesterolaemia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

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Children with hypercholesterolemia (Slovenia)

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

Lipid levels measurement

Intervention Type DIAGNOSTIC_TEST

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

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.

Lipid levels measurement

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

Genetic analysis

Intervention Type 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.

Lipid levels measurement

Intervention Type DIAGNOSTIC_TEST

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

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.

Genetic analysis

Intervention Type 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.

Lipid levels measurement

Intervention Type DIAGNOSTIC_TEST

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

Interventions

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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.

Intervention Type DIAGNOSTIC_TEST

Lipid levels measurement

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Medical Centre Ljubljana

OTHER

Sponsor Role collaborator

Kinderkrankenhaus auf der Bult

OTHER

Sponsor Role collaborator

University of Ljubljana, Faculty of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Urh Groselj, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Ljubljana, Faculty of Medicine

Olga Kordonouri, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Kinderkrankenhaus auf der Bult

Locations

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Children's Hospital AUF DER BULT

Hanover, , Germany

Site Status

UMC - University Children's Hospital Ljubljana

Ljubljana, , Slovenia

Site Status

Countries

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Germany Slovenia

References

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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.

Reference Type BACKGROUND
PMID: 23956253 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26009596 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31895433 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26361156 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30270075 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30496984 (View on PubMed)

Other Identifiers

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FHUniScreenPeds

Identifier Type: -

Identifier Source: org_study_id

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