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Impact of Genetic Testing on Low-density Lipoprotein Cholesterol in Patients with Familial Hypercholesterolemia (GenTLe-FH study)

Impact of Genetic Testing on Low-density Lipoprotein Cholesterol in Patients with Familial Hypercholesterolemia (GenTLe-FH study)

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We obtained written informed consent from 53 participants from April 2018. Then, we randomly allocated 50 patients to the intervention group (24 patients) or to the control (26 patients). Baseline characteristics of the study participants were as follows: mean age (intervention group, 54 years old vs. control group, 50), female (54% vs. 62%), BMI (median 23.7 vs. 23.0), hypertension (25% vs. 19%), diabetes mellitus (4% vs. 12%), Achilles tendon thickening (79% vs. 73%), family history of FH (50% vs. 69%), and causal variant positive (71% vs. 65%). The mean baseline LDL cholesterol levels were 132.7 mg/dL in the intervention group and 120.8 mg/dL in the control group.

Although we initially planned to recruit 100 participants, due to the COVID-19 pandemic from the beginning of 2020, it was challenging to obtain new study participants and regularly visit outpatient clinics. Therefore, the principal investigators and sub-investigators discussed and decided to terminate the enrollment of new subjects in April 2020. Finally, we completed the trial in November 2021.

A total of 19 adverse events occurred in both groups (6 in the intervention group and 13 in the control group), including one serious adverse event in the control group (unscheduled hospitalization for surgery for another disease [lipoma]). All the adverse events were not related to the intervention.

At week 24, mean changes of LDL-C from baseline were significantly larger in the intervention group than in control. Detailed results will be presented at the late-breaking clinical trial session at the 84th Annual Meeting of the Japanese Circulation Society on March 2022.

We obtained written informed consent from 53 participants from April 2018. Then, we randomly allocated 50 patients to the intervention group (24 patients) or to the control (26 patients). The mean baseline LDL cholesterol levels were 132.7 mg/dL in the intervention group and 120.8 mg/dL in the control group. At week 24, mean changes of LDL-C from baseline were significantly larger in the intervention group than in control.

Mar. 12, 2022

Mar. 12, 2022

No

N/A

https://jrct.mhlw.go.jp/latest-detail/jRCTs042180027

Nomura Akihiro

Kanazawa University

13-1 Takaramachi Kanazawa Ishikawa

anomura@med.kanazawa-u.ac.jp

Nomura Akihiro

Kanazawa University

13-1 Takaramachi Kanazawa Ishikawa

+81-76-265-2049

anomura@med.kanazawa-u.ac.jp

Complete

Oct. 02, 2017

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

We include the patients with all the following criteria:
1) Age equal or more than 15 years
2) Diagnosed with familial hypercholesterolemia per the criteria of the Japan
Atherosclerosis Society
3) Patients who have never got genetic tests, or have not yet returned genetic
results regarding familial hypercholesterolemia
4) Patients who can provide written informed consent

We exclude patients with either of the following criteria:
1) Liver dysfunction (AST or ALT > 3 times the UNL)
2) Renal dysfunction (Cr equal or more than 2.0 mg/dL)
3) Immunosuppression
4) Active cancer
5) Previous history of coronary heart disease:
i) Myocardial infarction
ii) History of percutaneous coronary intervention or coronary artery bypass graft
iii) Coronary stenosis (equal or more than 75%) previously detected by coronary angiography
6) Female with pregnancy or expected
7) Patients whose doctors in charge consider him/her inappropriate to participate

Both

Familial hypercholesterolemia

We will perform genetic counseling besides standard FH patient education. In addition, a single qualified doctor will inform genetically estimated future cardiovascular risk based on the result of genetic testing. Genetic counseling will comprise the following: (a) genetic diagnosis; (b) outline of what FH is; (c) checking family history of hyperlipidemia/cardiovascular diseases; (d) informing that the results of genetic testing could facilitate the research in this field; and (e) explaining the physical/mental support system in our hospital. Of note, this counseling will be provided by a qualified physician of clinical genetics. In addition, we will inform odds ratios of future cardiovascular risk, based on the presence or absence of 1) a causal genetic variant and 2) a clinical sign (xanthomas and/or family history of FH) by using the original Japanese documents (Supplemental Data 2).8 9 After counseling we will set time to answer the queries of patients adequately, confirming their level of understanding.

The plasma LDL cholesterol levels at 24 weeks

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 (PSQ-18) scores between the intervention and control groups or among the four groups taking genetic testing results (positive or negative) into consideration.

+81-76-265-2048

Nov. 29, 2018

None