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A Registration Study for Familial Hypercholesterolemia in Taiwan

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ClinicalTrials.gov Identifier: NCT03152656
Recruitment Status : Unknown
Verified September 2016 by National Taiwan University Hospital.
Recruitment status was:  Recruiting
First Posted : May 15, 2017
Last Update Posted : May 15, 2017
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:

Familial hypercholesterolemia (FH) is an inherited disorder of lipoprotein metabolism, transmitted in an autosomal dominant manner and clinically characterized by elevated levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol, the presence of tendon xanthomas, and premature atherosclerosis.

The homozygous form of familial hypercholesterolemia (HoFH) with autosomal dominant transmission, in which case both alleles of either LDLR, APOB, or PCSK9 gene are defective, is a rare genetic disorder with prevalence estimated to be one per million population.

Large scale genetic screening for active FH cases finding has been performed in the Netherlands, Spain, Norway and Wales. However, the FH population and prevalence in Taiwan have never been formally studied. Patients are usually not under appropriate treatment owing to lack of standardized diagnostic tool and treatment strategy for FH. Moreover, with the emerging of new classes of LLTs, including microsomal triglyceride transfer protein (MTP) inhibitor, antisense oligonucleotide inhibitor, and PCSK9 inhibitors, even homozygous FH patients now have better chance to be treated to reach recommended treatment goals. Therefore, A National FH registry is needed to collect contemporary data on diagnosis, treatment and outcomes with long- term goals of improving diagnosis, management, and reduction of unnecessary cardiovascular events in FH population in Taiwan.


Condition or disease
Familial Hypercholesterolemia

Detailed Description:

Familial hypercholesterolemia (FH) is an inherited disorder of lipoprotein metabolism, transmitted in an autosomal dominant manner and clinically characterized by elevated levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol, the presence of tendon xanthomas, and premature atherosclerosis.The genetic basis of FH is a large array of point mutations and large gene rearrangements in the LDL receptor (LDLR) gene, resulting in defective functional receptors for LDL on the cell surface, which are unable to clear plasma LDL and result in increased plasma LDL levels. Similarly, point mutations in the gene coding for apolipoprotein B (APOB) also reduce LDL clearance, resulting in the disorder familial defective apolipoprotein B, which is clinically indistinguishable from FH. In 2003, a third FH locus located on chromosome 1, encoding proprotein convertase subtilisin/kexin 9 (PCSK9) was identified. The phenotypes caused by mutations in LDLR, APOB, or PCSK9 are clinically indistinguishable and all characterized by elevated levels of plasma LDL cholesterol and premature coronary artery disease.

The homozygous form of familial hypercholesterolemia (HoFH) with autosomal dominant transmission, in which case both alleles of either LDLR, APOB, or PCSK9 gene are defective, is a rare genetic disorder with prevalence estimated to be one per million population. Patients with HoFH have an extremely rapid accumulation of atherosclerosis with most experiencing xanthomas and severe vascular disease by adolescence or early adulthood despite interventions, including LDL apheresis, which led to the recent Food and Drug Administration approval of 2 novel therapies, lomitapide and mipomersen, specifically for HoFH. Heterozygous familial hypercholesterolemia (HeFH), in which only one allele of LDLR, APOB or PCSK9 gene is defective, has a prevalence of approximately one in 500 individuals, making it one of the most common inherited disorders. Reduction of elevated cholesterol levels in FH individuals can result in a significant reduction of cardiovascular mortality and morbidity, as a large number of landmark clinical trials with cholesterol synthesis inhibitors have clearly demonstrated. However, less than 10% of patients with HeFH are diagnosed and less than 25% are treated with LDL-lowering medications.

Large scale genetic screening for active FH cases finding has been performed in the Netherlands, Spain, Norway and Wales. However, the FH population and prevalence in Taiwan have never been formally studied. Patients are usually not under appropriate treatment owing to lack of standardized diagnostic tool and treatment strategy for FH. Moreover, with the emerging of new classes of LLTs, including microsomal triglyceride transfer protein (MTP) inhibitor, antisense oligonucleotide inhibitor, and PCSK9 inhibitors, even homozygous FH patients now have better chance to be treated to reach recommended treatment goals. Therefore, A National FH registry is needed to collect contemporary data on diagnosis, treatment and outcomes with long- term goals of improving diagnosis, management, and reduction of unnecessary cardiovascular events in FH population in Taiwan.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1000 participants
Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration: 1 Year
Official Title: A Registration Study for Familial Hypercholesterolemia in Taiwan
Actual Study Start Date : July 2015
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Composite cardiovascular outcome [ Time Frame: 3 years ]
    The composite cardiovascular (CV) outcome will be any CV events (coronary, cerebral, or peripheral vascular diseases)


Secondary Outcome Measures :
  1. With at least 1 cardiovascular risk factor. [ Time Frame: 3 years ]
    no evidence of atherosclerotic vascular diseases,with at least 1 cardiovascular risk factor.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Potentially eligible patients will be invited for a screening visit. Written informed consent will be obtained from all patients, and the study will be approved by the institutional review board.

1000 Subjects (estimated) with diagnosis of definite or probable FH, including both heterozygous and homozygous FH, using Taiwan FH Diagnostic Criteria will be recruited for enrollment and clinically followed for at least three years. Taiwan FH Diagnostic Criteria was revised from Dutch Lipid Clinic Network (DLCN) Criteria with consensus of experts in cardiology, genetic, and metabolism specialty, and published by Taiwan Society of Lipids & Atherosclerosis in 2014.

Criteria

Inclusion Criteria:

  • Taiwan FH Diagnostic Criteria was revised from Dutch Lipid Clinic Network (DLCN) Criteria with consensus of experts in cardiology, genetic, and metabolism specialty, and published by Taiwan Society of Lipids & Atherosclerosis in 2014.

Exclusion Criteria:

  • The main exclusion criteria will be secondary causes of hyperlipidemia other than FH (i.e. untreated hypothyroidism, nephrotic syndrome), hemodynamically significant valvular or congenital heart disease, life-threatening malignancy, treatment with immunosuppressive agents, or any condition or situation which, in the opinion of the investigator, might be not suitable for this registration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03152656


Contacts
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Contact: Chau C Wu, M.D., Ph.D. 886-2-23123456 ext 88560 chauchungwu@ntu.edu.tw
Contact: Wan T Ke 886-2-23123456 ext 88558 ntuh33668810@gmail.com

Locations
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Taiwan
NTUH Recruiting
Taipei, Taiwan
Contact: Chau C Wu    886-2-23123456 ext 88560    chauchungwu@ntu.edu.tw   
Sub-Investigator: Wan T Ke         
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
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Principal Investigator: Chau C Wu, M.D., Ph.D. National Taiwan University Hospital

Additional Information:

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Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT03152656     History of Changes
Other Study ID Numbers: 201505031RIND
First Posted: May 15, 2017    Key Record Dates
Last Update Posted: May 15, 2017
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Taiwan University Hospital:
Familial hypercholesterolemia
total cholesterol
low-density lipoprotein cholesterol
tendon xanthomas
premature atherosclerosis
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type II
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias