NPC1L1 Gene Polymorphism and the Efficacy and Safety of Hybutimibe

The Association Between NPC1L1 Gene Polymorphism and the Efficacy and Safety of Hybutimibe in High/very High Risk ASCVD Patients

Significant individual differences may lead to differences in patients' responses to drug therapy and lead to an increased incidence of adverse reactions. However, there are currently very limited data on the genetic variation of the NPC1L1 gene in the Chinese population. In view of the important role of NPC1L1 gene polymorphism in cholesterol absorption, lipid profile, coronary heart disease prevalence and ezetimibe response, it is necessary to focus on the allele frequency analysis of NPC1L1 gene polymorphism in the Chinese population, and to further explore the therapeutic response of NPC1L1 gene polymorphism and Hybutimibe.

With reference to previous domestic and foreign literature reports and HapMap project (http://hapmap.ncbi.nlm. nih.gov/)SNP) distribution, this study selected NPC1L1 gene loci with relatively in-depth clinical research. rs2072183, rs4720470, rs2073547 were analyzed. The minimum allele frequency (MAF) of the above loci were all greater than 10%, and it has been confirmed that genetic variation exists between different diseases and different races, which may affect the lipid profile , the risk of coronary heart disease and the response to hybomaib treatment. However, the variability of rs2072183 in response to Hybutimibe needs to be further verified, and the effects of rs4720470 and rs2073547 gene polymorphisms on drug response also need to be targeted. In order to further determine the correlation between the distribution of NPC1L1 polymorphism and the efficacy and safety of Hybutimibe, we conducted this study to observe the distribution frequency of NPC1L1 gene polymorphisms at rs2072183, rs4720470 and rs2073547 in high-risk/extremely high-risk ASCVD patients. To explore the correlation between NPC1L1 gene polymorphisms and the efficacy and safety of Hybutimibe combined with moderate-intensity statins in the treatment of high-risk/very high-risk ASCVD patients. This is the first time to explore the distribution of NPC1L1 polymorphism in high/very high risk ASCVD population in China, which will provide genetic evidence for the correct use of Hybutimibe and moderate intensity statin therapy, and provide further evidence-based medical evidence for the distribution of NPC1L1 polymorphism and the efficacy and safety of Hybutimibe.

Study Overview

• Status: Not yet recruiting
• Conditions: ASCVD; Gene Polymorphism
• Intervention / Treatment: Drug: Hybutimibe 10mg QD

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: zhongsu Wang, Doctor; Phone Number: 15969694663; Email: wangzhongsu2016@163.com
• Study Contact Backup: Name: mei Gao, Doctor; Phone Number: 13791126569

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients at high/very high risk of ASCVD who were treated with only moderate-intensity statins for at least 8 weeks before enlistment and whose LDL-C levels did not meet the lipid reduction target corresponding to the risk stratification level of ASCVD recommended by the Chinese Lipid Management Guidelines (2023) and who needed to be combined with Hybutimibe.

Description

Inclusion Criteria:

1. Patients with high/very high risk of ASCVD were only treated with moderate intensity statins (including atorvastatin 10-20mg, rosuvastatin 5-10mg, fluvastatin 80mg, lovastatin 40mg, pivastatin 1-4mg, pravastatin 40mg, simvastatin 20-40mg, etc.) for at least 8 weeks before enlistment.
2. The LDL-C level did not meet the lipid reduction target corresponding to the risk stratification level of ASCVD recommended by the Chinese Lipid Management Guidelines (2023), or the level of LDL-C was still not up to the standard as clinicians expected that patients should continue to use medium-dose statins for lipid-lowering treatment alone, and the cholesterol absorption inhibitor Hybomab should be combined;
3. Age 18-75 years old;
4. BMI range 22-45 kg/m2;
5. Can understand and voluntarily sign informed consent.

Exclusion Criteria:

1. Allergic history of cholesterol absorption inhibitors and statins;
2. other types of cholesterol absorption inhibitors have been used;
3. Homozygous familial hypercholesterolemia;
4. any clinically serious endocrine disease affecting blood lipids or lipid proteins;
5. Abnormal liver function with AST or ALT greater than three times the upper limit of normal, or bilirubin >34uM, creatine muscle enzyme greater than five times the upper limit of normal, or evidence of serologically infectious liver disease;
6. Thyroid dysfunction;
7. History of malignant tumor;
8. Patients with coagulation dysfunction;
9. Women who are pregnant or planning to become pregnant;
10. Taking fenofibrate, gefilozil, probucol, warfarin, glucocorticoids, cyclosporine or another immunosuppressant within 30 days prior to the trial;
11. can not adhere to medication or regular follow-up;
12. Communication disorders, people with severe aphasia, audio-visual impairment, serious mental illness, and difficulty cooperating with investigators;
13. There are other circumstances that the researcher considers inappropriate to participate in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental group; Hybutimibe 10mg QD was added to the conventional treatment	Drug: Hybutimibe 10mg QD; Hybutimibe was added to the conventional treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of LDL-C change from baseline at week 12 of treatment	Rate of LDL-C change from baseline in high-risk/very high-risk ASCVD patients at week 12 of treatment	at week 12 of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
At the 4th week of treatment, LDL-C change rate from baseline in high-risk/very high-risk ASCVD patients	At the 4th week of treatment, LDL-C change rate from baseline in high-risk/very high-risk ASCVD patients	At the 4th week of treatment
Changes in HDL-C, TC and TG levels at the 4th and 12th week of treatment.	Changes in HDL-C, TC and TG levels at the 4th and 12th week of treatment.	at the 4th and 12th week of treatment
Changes in levels of alanine aminotransferase, aspartate aminotransferase and creatine kinase at the 4th and 12th week of treatment.	Changes in levels of alanine aminotransferase, aspartate aminotransferase and creatine kinase at the 4th and 12th week of treatment.	at the 4th and 12th week of treatment
Polymorphism and distribution frequency of NPC1L1 gene rs2072183, rs4720470 and rs2073547 in high-risk/extremely high-risk ASCVD patients.	Polymorphism and distribution frequency of NPC1L1 gene rs2072183, rs4720470 and rs2073547 in high-risk/extremely high-risk ASCVD patients.	at enrollment

Collaborators and Investigators

• Sponsor: Qianfoshan Hospital
• Collaborators: Beijing Micro Love Public Welfare Foundation
• Investigators: Study Chair: mei Gao, Doctor, The First Affiliated Hospital of Shandong First Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 11, 2024
• First Submitted That Met QC Criteria: October 11, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 11, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: YXLL-KY-2024（067)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No