Henagliflozin's Impact on Prediabetes Remission

NCT ID: NCT06448130

Last Updated: 2024-06-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

984 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-30

Study Completion Date

2027-12-31

Brief Summary

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This clinical trial evaluates the effectiveness of Henagliflozin combined with lifestyle interventions for managing patients with prediabetes. As global prediabetes rates rise, increasing the risk of diabetes and vascular issues, addressing treatment gaps is essential. Henagliflozin, a novel SGLT2 inhibitor developed in China, aims to improve glucose control and metabolic health when paired with lifestyle changes.

The study's primary objectives include: assessing whether Henagliflozin can achieve normoglycemia in prediabetic patients after 6 months of treatment.

The trial will compare three groups (Henagliflozin 5mg, 10mg, and a placebo), focusing on efficacy and safety. Participants, assigned randomly, will undergo a 6-month treatment phase and an 18-month follow-up. Regular health assessments will monitor glucose levels, metabolic health, and risks of major complications like cardiovascular events and microvascular diseases, with additional evaluations of C-peptide and insulin changes.

Structured as a multicenter, randomized, double-blind, placebo-controlled study, it involves 984 prediabetic adults across 50 medical institutions in China. This comprehensive approach could redefine prediabetes management by integrating drug therapy with lifestyle modifications.

Detailed Description

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This research is launched in light of the global surge in prediabetes, a condition that markedly increases the risk of developing type 2 diabetes and related vascular complications. While lifestyle modifications are the frontline defense against prediabetes, the variability in individual responses often requires the integration of pharmacological treatments. Studies have shown that drugs such as metformin, acarbose, SGLT2 inhibitors, GLP-1 agonists, GIP/GLP-1 receptor agonists, thiazolidinediones, and orlistat effectively curb the progression to diabetes. Yet, there remains a gap in specific research addressing the intervention needs of the prediabetic population in China.

Currently, acarbose is the only drug approved in the Chinese market for treating patients with impaired glucose tolerance, highlighting a limited range of therapeutic options for prediabetes. SGLT2 inhibitors, as a newer class of hypoglycemic agents, have demonstrated significant promise in reducing major cardiovascular events in high-risk patients with type 2 diabetes, enhancing outcomes in heart failure, and providing renal protection. However, there is a scarcity of large-scale, prospective studies on the impact of SGLT2 inhibitors in prediabetes. Henagliflozin, the first original SGLT2 inhibitor developed in China and launched on December 31, 2021, is being studied to assess its effectiveness combined with lifestyle interventions in the prediabetic demographic, aiming to fill a crucial void in the current treatment paradigm.

This study aims to assess the combined benefits of Henagliflozin and lifestyle modifications in managing prediabetes. The investigators conducted a two-year prospective, randomized, double-blind, placebo-controlled trial across 50 medical institutions in various provinces of China. It is planned to enroll 984 adult prediabetic patients who had not previously been treated with antidiabetic medications. Participants meeting inclusion criteria were randomly assigned to one of three groups: Henagliflozin 5mg, Henagliflozin 10mg, or placebo. The intensive intervention phase, consisting of pharmacotherapy combined with lifestyle changes, lasted for 6 months, followed by an 18-month follow-up period focusing solely on lifestyle interventions.

The primary endpoint is the proportion of participants achieving normoglycemia after 6 months of intervention, with subsequent assessments at 12 months. Secondary endpoints include short-term (0-12 months) and long-term (12-24 months) changes in glucose control, metabolic indicators such as body weight, body mass index (BMI), body fat content, waist and hip circumference, lipid profiles, blood pressure, serum uric acid levels, hepatic steatosis, and carotid intima-media thickness. Exploratory outcomes encompass changes in C-peptide and insulin levels from baseline to 6 months, and the risk of major adverse cardiovascular events (MACE) from baseline to 24 months and beyond.

Conditions

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PreDiabetes Prediabetic State Type 2 Diabetes Glucose Metabolism Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Henagliflozin5mg + lifestyle intervention

Henagliflozin 5mg+ placebo 10mg po qd + lifestyle intervention for 6 months

Group Type EXPERIMENTAL

Henagliflozin 5mg

Intervention Type DRUG

Henagliflozin 5mg + lifestyle intervention

Henagliflozin10mg+ lifestyle intervention

Henagliflozin 10mg+ placebo 5mg po qd + lifestyle intervention for 6 months

Group Type EXPERIMENTAL

Henagliflozin 10mg

Intervention Type DRUG

Henagliflozin 10mg+ lifestyle intervention

placebo+ lifestyle intervention

placebo 10mg + placebo 5mg po qd + lifestyle intervention for 6 months

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo+ lifestyle intervention

Interventions

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Henagliflozin 5mg

Henagliflozin 5mg + lifestyle intervention

Intervention Type DRUG

Henagliflozin 10mg

Henagliflozin 10mg+ lifestyle intervention

Intervention Type DRUG

Placebo

Placebo+ lifestyle intervention

Intervention Type DRUG

Other Intervention Names

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lifestyle intervention lifestyle intervention lifestyle intervention

Eligibility Criteria

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Inclusion Criteria

1. Male or female subjects between the ages of 18 and 65 years;
2. Individuals without hypoglycemic therapy before, including hypoglycemic drugs or traditional Chinese medicine formulations with hypoglycemic effects;
3. Prediabetic patients as defined by Expert Consensus on Intervention for Prediabetes in Chinese Adults, 2023 Edition:1)Fasting plasma glucose (FPG) between 6.1 and 7.0 mmol/L and/or 2-hour postprandial glucose (2h-PPG) between 7.8 and 11.1 mmol/L; 2)And/or HbA1c between 5.7% and 6.5%;
4. Individuals willing to provide written informed consent and can comply with study procedures and follow-up.

Exclusion Criteria

1. Allergic to Henagliflozin;
2. Previously diagnosed with diabetes;
3. HbA1c ≥ 6.5% or FPG ≥ 7.0 mmol/L or PPG ≥ 11.1 mmol/L;
4. Use of GLP-1 receptor agonists, orlistat, or other weight-reducing drugs in the past 3 months;
5. Fluctuation in weight by 5% or more in the past month;
6. Use of drugs affecting glucose synthesis, absorption, or metabolism, such as glucocorticoids (e.g., prednisone, dexamethasone), contraceptives, growth hormone, hormonal replacement therapy (estrogen and progesterone), immunosuppressants (e.g., cyclosporine A, tacrolimus), anti-tuberculosis drugs (e.g., isoniazid, rifampicin);
7. Untreated hyperthyroidism or hypothyroidism, excluding those with normal thyroid function after treatment;
8. Persistently uncontrolled hypertension (used antihypertensive drugs but was not effectively controlled in the 3 months prior to enrollment) or currently use 3 or more antihypertensive drugs (including diuretics);
9. Assessed by the investigator to be at high risk of genitourinary system infections, such as history of recurrent urinary tract infections or reproductive system infections, long-term placement of urinary catheters, or history of urological surgery;
10. Other obesity caused by endocrine disorders, such as Cushing's syndrome;
11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels \> 3 times of the upper limit of the normal range (UNL);
12. eGFR less than 30 mL/min/1.73 m2, severe kidney damage, end-stage renal disease or requiring dialysis;
13. Significant cardiovascular diseases including myocardial infarction, congestive heart failure (≥grade III New York Heart Association), left ventricular ejection fraction≤40%, or cerebrovascular accidents;
14. Impaired consciousness and various mental health disorders;
15. Malignant tumors and other serious illnesses;
16. Pregnant or breast-feeding or planning pregnancy within 24 months;
17. Enrolled in another clinical trial currently or within the 3 months prior to enrollment;
18. Identified by the investigator that lacks sufficient motivation to continue the long-term clinical trial (e.g., out-of-town study, work plan, need to care for family members), or considered prefer to withdraw from the trial for non-medical reasons (such as social issues).
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shandong Provincial Hospital

OTHER_GOV

Sponsor Role lead

Responsible Party

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Jia-jun Zhao

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Chuzhou First People's Hospital

Chuzhou, Anhui, China

Site Status

The First Affiliated Hospital of University of Science and Technology of China

Hefei, Anhui, China

Site Status

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Site Status

Fujian Provincial Hospital

Fuzhou, Fujian, China

Site Status

LanZhou University

Lanzhou, Gansu, China

Site Status

Shunde Hospital of Southern Medical University

Foshan, Guangdong, China

Site Status

Southern Medical University

Guangzhou, Guangdong, China

Site Status

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Guanzhou, Guangdong, China

Site Status

Shenzhen Second People's Hospital

Shenzhen, Guangdong, China

Site Status

First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

Site Status

North China University of Technology Affiliated Hospital

Tangshan, Hebei, China

Site Status

The Second Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Site Status

Xinyang Central Hospital

Xinyang, Henan, China

Site Status

First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status

Tongji Hospital

Wuhan, Hubei, China

Site Status

Xiangyang Central Hospital

Xiangyang, Hubei, China

Site Status

Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status

The Second Affiliated Hospital of Baotou Medical College

Baotou, Inner Mongolia, China

Site Status

Second Affiliated Hospital of Nanchang University

Nanchang, Jiangsu, China

Site Status

The First Affiliated Hospital with Nanjing Medical University,

Nanjing, Jiangsu, China

Site Status

Wuxi People's Hospital

Wuxi, Jiangsu, China

Site Status

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Site Status

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status

The First Hospital of Jilin University

Changchun, Jilin, China

Site Status

First Affiliated Hospital of China Medical University

Shenyang, Liaoning, China

Site Status

People's Hospital of Liaoning Province

Shenyang, Liaoning, China

Site Status

Ningxia Medical University

Yinchuan, Ningxia, China

Site Status

Binzhou City Central Hospital

Binzhou, Shandong, China

Site Status

Dongying People's Hospital

Dongying, Shandong, China

Site Status

Jinan Central Hospital

Jinan, Shandong, China

Site Status

Shandong Provincial Hospital Affiliated to Shandong First Medical University

Jinan, Shandong, China

Site Status

Liaocheng People's Hospital

Liaocheng, Shandong, China

Site Status

The Second Affiliated Hospital of Shandong First Medical University

Tai’an, Shandong, China

Site Status

The Affiliated Hospital of Weifang Medical University

Weifang, Shandong, China

Site Status

Weifang People's Hospital

Weifang, Shandong, China

Site Status

Yantai Affiliated Hospital of Binzhou Medical University

Yantai, Shandong, China

Site Status

Affiliated Hospital of Southwest Medical University

Luzhou, Sichuan, China

Site Status

First Affiliated Hospital of Xinjiang Medical University

Ürümqi, Xinjiang, China

Site Status

The Central Hospital of Lishui City

Lishui, Zhejiang, China

Site Status

First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Site Status

Wenzhou Central Hospital

Wenzhou, Zhejiang, China

Site Status

Beijing Hospital

Beijing, , China

Site Status

Beijing Luhe Hospital

Beijing, , China

Site Status

Beijing Chao Yang Hospital

Beijing, , China

Site Status

First Affiliated Hospital of Chongqing Medical University

Chongqing, , China

Site Status

Baoshan Hospital of Integrated Traditional Chinese and Western Medicine

Shanghai, , China

Site Status

Shanghai 10th People's Hospital

Shanghai, , China

Site Status

Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Shanghai, , China

Site Status

Peking University Binhai Hospital

Tianjin, , China

Site Status

Tianjin First Central Hospital

Tianjin, , China

Site Status

Countries

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China

Central Contacts

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Xiude Fan, MD&PhD

Role: CONTACT

+8613186067538

Junming Han, PhD

Role: CONTACT

+8615610140319

Facility Contacts

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Gaofei Ren, MD

Role: primary

+8615890688469

Xiude Fan

Role: primary

+8613186067538

Dong Zhao, MD

Role: primary

+8618911598827

Other Identifiers

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MA-DM-IV-004

Identifier Type: -

Identifier Source: org_study_id

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