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Impact of genetic testing on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia (GenTLe-FH): a randomised waiting list controlled open-label study protocol
  1. Akihiro Nomura1,2,
  2. Hayato Tada1,
  3. Hirofumi Okada1,
  4. Atsushi Nohara1,
  5. Hideki Ishikawa3,
  6. Kenichi Yoshimura2,
  7. Masa-aki Kawashiri1
  1. 1 Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
  2. 2 Innovative Clinical Research Center, Kanazawa University (iCREK), Kanazawa, Ishikawa, Japan
  3. 3 Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan
  1. Correspondence to Dr Hayato Tada; ht240z{at}sa3.so-net.ne.jp

Abstract

Introduction Familial hypercholesterolemia (FH) is an autosomal-dominant inherited genetic disease. High-throughput sequencing quickly and comprehensively detects causative variants of FH-related genes (LDLR, PCSK9, APOB and LDLRAP1). Although the presence of causative variants in FH-related genes correlates with future cardiovascular events, it remains unclear whether detection of causative gene mutation and disclosure of its associated cardiovascular risk affects outcomes in patients with FH. Therefore, this study intends to evaluate the efficacy of counselling future cardiovascular risk based on genetic testing in addition to standard patients’ education programme in patients with FH.

Methods and analysis A randomised, waiting-list controlled, open-label, single-centre trial will be conducted. We will recruit patients with clinically diagnosed FH without previous history of coronary heart disease from March 2018 to December 2019, and we plan to follow up participants until March 2021. For the intervention group, we will perform genetic counselling and will inform an estimated future cardiovascular risk based on individuals’ genetic testing results. The primary endpoint of this study is the plasma low-density lipoprotein cholesterol level at 24 weeks after randomisation. The secondary endpoints assessed at 24 and 48 weeks are as follows: blood test results; smoking status; changes of lipid-lowering agents’ regimen and Patients Satisfaction Questionnaire Short Form scores among the four groups divided by the presence of genetic counselling and genetic status of FH.

Ethics and dissemination This study will be conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects and all other applicable laws and guidelines in Japan. This study protocol was approved by the IRB at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal.

Trial registration number UMIN000029375.

  • familial hypercholesterolemia
  • genetic testing
  • genetic counseling
  • cardiovascular risk

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Patient consent for publication Not required.

  • Contributors AN, HT, HO, AN and M-aK designed and conducted the study. KY and HI gave us critical comments on statistical methods. All authors performed a critical review and approved the final version of the manuscript.

  • Funding This study is supported by the Innovative Clinical Research Center Kanazawa University (iCREK) Clinical Research Seed Grant.

  • Competing interests None declared.

  • Ethics approval This study protocol (V.2.0, dated 27 August 2018) was approved by the Institutional Review Board at Kanazawa University Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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