Effect of UDCA on the New Onset Diabetes and Glucose Intolerance Induced by Statin

Effect of UDCA on the New Onset Diabetes and Glucose Intolerance Induced by Statin-A Multicenter, Prospective, Random Controlled Trial

At present, it is recognized that statins are the cornerstone of treatment for the prevention of major cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD); However, at the same time, the increased risk of long-term glucose tolerance and type 2 diabetes mellitus caused by statin therapy has attracted wide attention. The investigators' recent study found that the levels of glycosylated hemoglobin, insulin and C-peptide increased significantly with the extension of follow-up time in patients with hyperlipidemia. At the same time, serum and fecal bile acid metabolism profiles, especially secondary bile acid metabolism, were extensively changed, especially in ursodeoxycholic acid (UDCA), suggesting that the decrease of UDCA is a possible mechanism for statins to induce side effects of diabetes. According to this hypothesis, ursodeoxycholic acid combined with statins may improve the abnormal glucose tolerance caused by statins and maximize the benefit of statins. This study is a multicenter, prospective, randomized, parallel, double-blind placebo-controlled, cohort study. Taking ASCVD patients as the research object, the investigators will compare the changes of glycosylated hemoglobin, fasting blood glucose, fasting insulin, C-peptide and metabolomic indexes before and after the use of ursodeoxycholic acid combined with atorvastatin and atorvastatin alone and during follow-up, Further evaluate the changes of blood glucose related indexes before and after the use of ursodeoxycholic acid combined with atorvastatin and atorvastatin alone, clarify the possible mechanism and specific treatment targets of abnormal glucose tolerance caused by statin, and put forward a possible alternative treatment for the disorder of glucose metabolism caused by statin.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: UDCA

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jianqing She; Phone Number: 17782959686; Email: jianqingshe@xjtu.edu.cn

Study Locations

• China
  • Shanxi
    • Xi'an, Shanxi, China
      • Recruiting
      • First Affiliated Hospital of Xi'an JiaoTong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years old and < 80 years old, regardless of gender;
• For those who had indications for taking statins for more than half a year, glycosylated hemoglobin increased by more than 0.5 and > 6.1% compared with half a year ago;
• Agree to accept the study treatment plan and voluntarily sign the informed consent form.

Exclusion Criteria:

• previous diagnosis of diabetes mellitus;
• Received hypoglycemic drug treatment;
• The level of abdominal blood glucose at baseline was ≥ 7mmol / L;
• Need to take glucocorticoids for a long time;
• Acute myocardial infarction and stroke occurred in the last 6 months;
• Severe liver dysfunction;
• Glomerular filtration rate (EGFR) < 30ml / min / 1.73m2 (MDRD formula);
• Malignant tumor;
• Blood system diseases;
• Acute or severe systemic infection;
• Women during pregnancy, lactation and preparation for pregnancy;
• Alcohol and other drug addicts and mental patients;
• Patients who are participating in other clinical studies or withdraw from less than 1 month;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: UDCA 500mg per day; This group of participants receive UDCA 500mg per day.	Drug: UDCA; UDCA vs. placebo together with statin in ASCVD patients; Other Names: Ursodeoxycholic acid
Placebo Comparator: Placebo; This group of participants receive placebo.	Drug: UDCA; UDCA vs. placebo together with statin in ASCVD patients; Other Names: Ursodeoxycholic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of HbA1c	Changes of glycosylated hemoglobin after taking ursodeoxycholic acid for half a year	12 months after enrollment

Secondary Outcome Measures

Outcome Measure	Time Frame
Concentration of blood lipid	12 months after enrollment
Concentration of fasting blood glucose	12 months after enrollment
Concentration of fasting islets	12 months after enrollment
Concentration of bile acids	12 months after enrollment
Rate of MACE	12 months after enrollment

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Investigators: Study Chair: Zuyi Yuan, First Affiliated Hospital Xi'an Jiaotong University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 10, 2021
• First Submitted That Met QC Criteria: August 11, 2022
• First Posted (Actual): August 15, 2022

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Diabetes Mellitus; Glucose Intolerance; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: XJTU1AF2021CRF-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No