Clinical trial NCT06448130: Henagliflozin's Impact on Prediabetes Remission
Official title: Effect of Henagliflozin on the Remission of Prediabetes Population: A National Multicenter, Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: PreDiabetes
Prediabetic State
Type 2 Diabetes
Glucose Metabolism Disorders
Keywords: Prediabetes management
Henagliflozin
SGLT2 inhibitors
Lifestyle interventions
Type 2 diabetes prevention
Glucose Metabolism Disorders
Metabolic Diseases
Lead sponsor: Shandong Provincial Hospital
Sponsor class: OTHER_GOV
First posted: 2024-06-07
Enrollment: 984
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Normoglycemia Achievement Rates Post-6-Month Intervention
timeFrame: From 6 months post-intervention to 12 months
Secondary outcomes:
measure: Blood Glucose Control Normalization
timeFrame: From 6 months post-intervention to 24 months
measure: Incidence of New-Onset Type 2 Diabetes
timeFrame: From 0 to 24 months
measure: Changes in HbA1c Levels
timeFrame: From 0 to 24 months
measure: Impact of Glycemic Status at 12 Months
timeFrame: From 12 months to 24 months
measure: Changes in blood pressure over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in serum uric acid levels over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in hepatic steatosis over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in carotid intima-media thickness over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in Total Cholesterol (TC) over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in Triglycerides (TG) over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in Low-Density Lipoprotein Cholesterol (LDL-c) over 24 Month
timeFrame: From 0 to 24 months
measure: Changes in High-Density Lipoprotein Cholesterol (HDL-c) over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in Body Weight over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in Body Mass Index (BMI) over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in Body Fat Content over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in Waist Circumference over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in Hip Circumference over 24 Months
timeFrame: From 0 to 24 months
measure: Changes in C-peptide Levels over the First 6 Months
timeFrame: From 0 to 6 months
measure: Changes in Insulin Levels over the First 6 Months
timeFrame: From 0 to 6 months
measure: Major Adverse Cardiovascular Events
timeFrame: From 0 to 24 months
measure: Risk of Retinal Diseases
timeFrame: From 0 to 24 months
measure: Risk of Renal diseases
timeFrame: From 0 to 24 months
Other outcomes:
Locations:
city: Chuzhou
country: China
facility: Chuzhou First People's Hospital
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of University of Science and Technology of China
state: Anhui
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Fuzhou
country: China
facility: Fujian Provincial Hospital
state: Fujian
city: Lanzhou
country: China
facility: LanZhou University
state: Gansu
city: Foshan
country: China
facility: Shunde Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Southern Medical University
state: Guangdong
city: Guanzhou
country: China
facility: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Second People's Hospital
state: Guangdong
city: Nanning
country: China
facility: First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Tangshan
country: China
facility: North China University of Technology Affiliated Hospital
state: Hebei
city: Ha'erbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Xinyang
country: China
facility: Xinyang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Baotou
country: China
facility: The Second Affiliated Hospital of Baotou Medical College
state: Inner Mongolia
city: Nanchang
country: China
facility: Second Affiliated Hospital of Nanchang University
state: Jiangsu
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University,
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: First Affiliated Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: People's Hospital of Liaoning Province
state: Liaoning
city: Yinchuan
country: China
facility: Ningxia Medical University
state: Ningxia
city: Binzhou
country: China
facility: Binzhou City Central Hospital
state: Shandong
city: Dongying
country: China
facility: Dongying People's Hospital
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Hospital Affiliated to Shandong First Medical University
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Tai'an
country: China
facility: The Second Affiliated Hospital of Shandong First Medical University
state: Shandong
city: Weifang
country: China
facility: The Affiliated Hospital of Weifang Medical University
state: Shandong
city: Weifang
country: China
facility: Weifang People's Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Affiliated Hospital of Binzhou Medical University
state: Shandong
city: Luzhou
country: China
facility: Affiliated Hospital of Southwest Medical University
state: Sichuan
city: Ürümqi
country: China
facility: First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Lishui
country: China
facility: The Central Hospital of Lishui City
state: Zhejiang
city: Wenzhou
country: China
facility: First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou Central Hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Beijing Luhe Hospital
city: Beijing
country: China
facility: Beijing Chao Yang Hospital
city: Chongqing
country: China
facility: First Affiliated Hospital of Chongqing Medical University
city: Shanghai
country: China
facility: Baoshan Hospital of Integrated Traditional Chinese and Western Medicine
city: Shanghai
country: China
facility: Shanghai 10th People's Hospital
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
city: Tianjin
country: China
facility: Peking University Binhai Hospital
city: Tianjin
country: China
facility: Tianjin First Central Hospital
Study officials:
References: