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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06448130
Other study ID # MA-DM-IV-004
Secondary ID
Status Not yet recruiting
Phase Phase 4
First received
Last updated
Start date June 2024
Est. completion date December 2027

Study information

Verified date June 2024
Source Shandong Provincial Hospital
Contact Xiude Fan, MD&PhD
Phone +8613186067538
Email fanxiudexjtu@163.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 984
Est. completion date December 2027
Est. primary completion date December 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility 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).

Study Design


Intervention

Drug:
Henagliflozin 5mg
Henagliflozin 5mg + lifestyle intervention
Henagliflozin 10mg
Henagliflozin 10mg+ lifestyle intervention
Placebo
Placebo+ lifestyle intervention

Locations

Country Name City State
China The Second Affiliated Hospital of Baotou Medical College Baotou Inner Mongolia
China Beijing Chao Yang Hospital Beijing
China Beijing Hospital Beijing
China Beijing Luhe Hospital Beijing
China Binzhou City Central Hospital Binzhou Shandong
China The First Hospital of Jilin University Changchun Jilin
China Xiangya Hospital of Central South University Changsha Hunan
China First Affiliated Hospital of Chongqing Medical University Chongqing
China Chuzhou First People's Hospital Chuzhou Anhui
China Dongying People's Hospital Dongying Shandong
China Shunde Hospital of Southern Medical University Foshan Guangdong
China Fujian Medical University Union Hospital Fuzhou Fujian
China Fujian Provincial Hospital Fuzhou Fujian
China Southern Medical University Guangzhou Guangdong
China Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guanzhou Guangdong
China The Second Affiliated Hospital of Harbin Medical University Ha'erbin Heilongjiang
China The First Affiliated Hospital of University of Science and Technology of China Hefei Anhui
China Jinan Central Hospital Jinan Shandong
China Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong
China LanZhou University Lanzhou Gansu
China Liaocheng People's Hospital Liaocheng Shandong
China The Central Hospital of Lishui City Lishui Zhejiang
China Affiliated Hospital of Southwest Medical University Luzhou Sichuan
China Second Affiliated Hospital of Nanchang University Nanchang Jiangsu
China The First Affiliated Hospital of Nanchang University Nanchang Jiangxi
China The First Affiliated Hospital with Nanjing Medical University, Nanjing Jiangsu
China First Affiliated Hospital of Guangxi Medical University Nanning Guangxi
China Baoshan Hospital of Integrated Traditional Chinese and Western Medicine Shanghai
China Shanghai 10th People's Hospital Shanghai
China Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University Shanghai
China First Affiliated Hospital of China Medical University Shenyang Liaoning
China People's Hospital of Liaoning Province Shenyang Liaoning
China Shenzhen Second People's Hospital Shenzhen Guangdong
China The Second Affiliated Hospital of Shandong First Medical University Tai'an Shandong
China North China University of Technology Affiliated Hospital Tangshan Hebei
China Peking University Binhai Hospital Tianjin
China Tianjin First Central Hospital Tianjin
China First Affiliated Hospital of Xinjiang Medical University Ürümqi Xinjiang
China The Affiliated Hospital of Weifang Medical University Weifang Shandong
China Weifang People's Hospital Weifang Shandong
China First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang
China Wenzhou Central Hospital Wenzhou Zhejiang
China Tongji Hospital Wuhan Hubei
China Wuxi People's Hospital Wuxi Jiangsu
China Xiangyang Central Hospital Xiangyang Hubei
China Xinyang Central Hospital Xinyang Henan
China The Affiliated Hospital of Xuzhou Medical University Xuzhou Jiangsu
China Yantai Affiliated Hospital of Binzhou Medical University Yantai Shandong
China Ningxia Medical University Yinchuan Ningxia
China First Affiliated Hospital of Zhengzhou University Zhengzhou Henan

Sponsors (1)

Lead Sponsor Collaborator
Shandong Provincial Hospital

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Normoglycemia Achievement Rates Post-6-Month Intervention This measure assesses the proportion of participants who achieve normoglycemia from the end of a 6-month intervention until the 12-month assessment point. Normoglycemia is defined as fasting plasma glucose (FPG) less than 6.1 mmol/L and 2-hour post-prandial glucose (2h-PPG) less than 7.8 mmol/L. The measure includes rates of sustained remission (normal glycemic status lasting more than 6 months post-medication cessation), partial remission (lasting 3-6 months), and temporary remission (lasting less than 3 months). From 6 months post-intervention to 12 months
Secondary Blood Glucose Control Normalization Proportion and duration of normalization of blood glucose levels within 24 months in the three study groups. From 6 months post-intervention to 24 months
Secondary Incidence of New-Onset Type 2 Diabetes Incidence of new-onset type 2 diabetes within 24 months in the three study groups. From 0 to 24 months
Secondary Changes in HbA1c Levels Changes in HbA1c levels over the 24-month period in the three study groups. From 0 to 24 months
Secondary Impact of Glycemic Status at 12 Months Impact of glycemic status at 12 months on subsequent reversal to normoglycemia and risk of new-onset type 2 diabetes during the 12-24 month follow-up period in the three study groups. From 12 months to 24 months
Secondary Changes in blood pressure over 24 Months Changes in systolic and diastolic blood pressure in the three study groups over 24 Months. From 0 to 24 months
Secondary Changes in serum uric acid levels over 24 Months Changes in serum uric acid levels in the three study groups over 24 Months. From 0 to 24 months
Secondary Changes in hepatic steatosis over 24 Months Changes in hepatic steatosis assessed by abdominal ultrasound in the three study groups over 24 Months. From 0 to 24 months
Secondary Changes in carotid intima-media thickness over 24 Months Changes in carotid intima-media thickness measured by carotid ultrasound in the three study groups over 24 Months. From 0 to 24 months
Secondary Changes in Total Cholesterol (TC) over 24 Months Measurement of Total Cholesterol (TC) levels in millimoles per liter (mmol/L) using standardized laboratory procedures. Fasting blood samples will be collected at multiple time points within the 24-month period to assess changes over time. From 0 to 24 months
Secondary Changes in Triglycerides (TG) over 24 Months Measurement of Triglycerides (TG) levels in millimoles per liter (mmol/L) using standardized laboratory procedures. Fasting blood samples will be collected at multiple time points within the 24-month period to assess changes over time. From 0 to 24 months
Secondary Changes in Low-Density Lipoprotein Cholesterol (LDL-c) over 24 Month Measurement of Low-Density Lipoprotein Cholesterol (LDL-c) levels in millimoles per liter (mmol/L) using standardized laboratory procedures. Fasting blood samples will be collected at multiple time points within the 24-month period to assess changes over time. From 0 to 24 months
Secondary Changes in High-Density Lipoprotein Cholesterol (HDL-c) over 24 Months Measurement of High-Density Lipoprotein Cholesterol (HDL-c) levels in millimoles per liter (mmol/L) using standardized laboratory procedures. Fasting blood samples will be collected at multiple time points within the 24-month period to assess changes over time. From 0 to 24 months
Secondary Changes in Body Weight over 24 Months Measurement of body weight in kilograms (kg) at multiple time points within the 24-month period. From 0 to 24 months
Secondary Changes in Body Mass Index (BMI) over 24 Months Calculation of BMI in kg/m² using the formula: weight (kg) / (height (m)²), measured at multiple time points within the 24-month period. From 0 to 24 months
Secondary Changes in Body Fat Content over 24 Months Measurement of body fat content as a percentage (%) of total body weight at multiple time points within the 24-month period. From 0 to 24 months
Secondary Changes in Waist Circumference over 24 Months Measurement of waist circumference in centimeters (cm) at multiple time points within the 24-month period. From 0 to 24 months
Secondary Changes in Hip Circumference over 24 Months Measurement of hip circumference in centimeters (cm) at multiple time points within the 24-month period. From 0 to 24 months
Secondary Changes in C-peptide Levels over the First 6 Months Measurement of C-peptide levels in nanomoles per liter (nmol/L) at multiple time points within the 6-month period. From 0 to 6 months
Secondary Changes in Insulin Levels over the First 6 Months Measurement of insulin levels in milliunits per liter (mU/L) at multiple time points within the 6-month period. From 0 to 6 months
Secondary Major Adverse Cardiovascular Events Major Adverse Cardiovascular Events (MACE) in the three study groups over 0-24 months. From 0 to 24 months
Secondary Risk of Retinal Diseases Risk of retinal diseases (e.g., diabetic retinopathy) in the three study groups over 0-24 months. From 0 to 24 months
Secondary Risk of Renal diseases Risk of renal diseases (e.g., diabetic nephropathy/chronic kidney disease) in the three study groups over 0-24 months. From 0 to 24 months
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