Efficacy of Henagliflozin for Weight Loss in Obesity Without Diabetes

Weight Loss Clinical Trial

Official title:

Efficacy of Henagliflozin for Weight Loss in Obesity Without Diabetes: a Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06216340
• Other study ID #: 2023-science-150
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: February 15, 2024
• Est. completion date: October 1, 2026

Study information

• Verified date: January 2024
• Source: The First People's Hospital of Changzhou
• Contact: Fei Hua, PHD
• Phone: +86-0519-68876242
• Email: huafei1970[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in China. The purpose of the 24-week trial is to investigate the efficacy of henagliflozin to induce body weight loss and the purpose of the extension is to evaluate the hypoglycemic effect of henagliflozin in obese subjects without diabetes.

Trial has the following two periods: 1) A 12-week randomized, double-blind, placebo-controlled, multi-center trial for evaluating the efficacy of henagliflozin to induce body weight loss; 2) A 12-week multicenter randomized controlled open-label trial for evaluating the hypoglycemic effect of henagliflozin followed by a 24-week extension period.

Description:

Primary Hypothesis:

The 12-week henagliflozin taking could induce significantly higher weight loss in obese subjects without diabetes, compared to diet-exercise therapy.

Assessment time points:

Baseline: prior to taking henagliflozin or diet-exercise therapy V1: 4 weeks following the henagliflozin taking or diet-exercise therapy V2: 4 weeks following V1 V3: 4 weeks following V2

Specific Aims 1:

To examine and compare the weight loss, assessed by weight, waist circumference, hip circumference and BMI, after 12-week henagliflozin taking or diet-exercise therapy in obese without diabetes.

Specific Aims 2:

To examine and compare the change of glucose level after 12-week henagliflozin taking or diet-exercise therapy in obese without diabetes.

Secondary Hypothesis 1:

The 24-week henagliflozin taking could siginificantly improve the glucose control in obese subjects with pre-diabetes, compared to diet-exercise therapy.

Assessment time points:

Baseline: prior to taking henagliflozin or diet-exercise therapy V4: 12 weeks following V3

Specific Aims:

To examine and compare the change of glucose level, assessed by fasting plasma glucose (FPG), postprandial plasma glucose (PPG), HbA1c, insulin levels, after 24-week henagliflozin taking or diet-exercise therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: October 1, 2026
• Est. primary completion date: October 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. 18 years old=age=65 years old, regardless of gender and race

2. Nondiabetic population: without hypoglycemic treatment, FPG<7.0 mmol/l, PPG<11.1 mmol/l, and HbA1c<6.5%

3. obesity: BMI=28 kg/m2

4. Stable weight: weight change less than 5kg in the past 3 months

5. Ability to understand and sign the informed consent form

Exclusion Criteria:

1. Allergies to Henagliflozin or its formulations;

2. Participants have been definitely diagnosed with diabetes;

3. HbA1c=6.5 % or FPG=7.0 mmol/l, or PPG=11.1 mmol/l;

4. Participants have used glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose linked transporter-2 (SGLT-2) inhibitors, or other weight loss related drugs within the past 3 months;

5. History of bariatric surgery;

6. Untreated or uncontrolled hypothyroidism/hyperthyroidism;

7. High risk of urinary tract infection;

8. Obesity induced by other endocrinologic disorders (e.g. Cushing's Syndrome);

9. Diagnosis of congenital glucose-galactose malabsorption or familial renal glycosuria

10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 2.5 times the upper limit of the normal range (UNL); Total bilirubin (TBIL) = 2.0 times the upper limit of the normal range;

11. estimated glomerular filtration rate (eGFR)<30 mL/min/1.73 m2 or end-stage kidney disease, or requiring dialysis;

12. History of major depressive disorder or other severe psychiatric disorders, e.g. schizophrenia, bipolar disorder within the last 2 years;

13. Uncontrolled treated/untreated hypertension (systolic blood pressure =160 mm Hg and/or diastolic blood pressure =100 mm Hg)

14. myocardial infarction, unstable angina, revascularization surgery, or cerebrovascular diseases within the past 3 months;

15. Cancer (past or present, except basal cell skin cancer or squamous cell skin cancer) or other severe diseases, which in the investigator's opinion could interfere with the results of the trial;

16. Females of child-bearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice) within 24 months;

17. Participation in a clinical trial within the last 3 months prior to screening;

18. Previous history of gestational diabetes;

19. Previous history of eating disorders;

20. Current or history of treatment with medications that may cause significant weight gain, within 3 months prior to screening, including systemic corticosteroids (except for a short course of treatment, i.e. 7-10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g. imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium);

21. Diet attempts using herbal supplements or over-the-counter medications within 3 months before screening

22. Any lifetime history of a suicidal attempt or a history of any suicidal behavior in the last month prior to randomization;

23. Surgery scheduled for the trial duration period, except for minor surgical procedures, at the discretion of the investigator

24. Known or suspected abuse of alcohol or narcotics

25. Subjects from the same house hold participating in the trial

26. Other situations which were inappropriate to the trial, at the discretion of the investigator

Related Conditions & MeSH terms

• Body Weight
• Diabetes Mellitus
• Obese
• Pre-diabetes
• Prediabetic State
• Weight Loss

Intervention

Drug:
• Henagliflozin
10mg of Henagliflozin and diet-exercise therapy
• Placebo
Placebo and diet-exercise therapy

Locations

Country	Name	City	State
n/a

Sponsors (10)

Lead Sponsor

Collaborator

The First People's Hospital of Changzhou

Affiliated Hospital of Jiangsu University, Northern Jiangsu People's Hospital, Second Affiliated Hospital of Soochow University, The Affiliated Hospital of Xuzhou Medical University, The First Affiliated Hospital of Soochow University, The First People's Hospital of Lianyungang, The fourth affiliated hospital of nantong university, The Second Hospital of Nanjing Medical University, Wuxi People's Hospital

References & Publications (6)

American Diabetes Association Professional Practice Committee. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45(Suppl 1):S17-S38. doi: 10.2337/dc22-S002. — View Citation

Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, Nadolsky K, Pessah-Pollack R, Plodkowski R; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITYEXECUTIVE SUMMARYComplete Guidelines available at https://www.aace.com/publications/guidelines. Endocr Pract. 2016 Jul;22(7):842-84. doi: 10.4158/EP161356.ESGL. — View Citation

Wang Y, Mi J, Shan XY, Wang QJ, Ge KY. Is China facing an obesity epidemic and the consequences? The trends in obesity and chronic disease in China. Int J Obes (Lond). 2007 Jan;31(1):177-88. doi: 10.1038/sj.ijo.0803354. Epub 2006 May 2. — View Citation

Wang Y, Xue H, Sun M, Zhu X, Zhao L, Yang Y. Prevention and control of obesity in China. Lancet Glob Health. 2019 Sep;7(9):e1166-e1167. doi: 10.1016/S2214-109X(19)30276-1. No abstract available. — View Citation

Wang Y, Zhao L, Gao L, Pan A, Xue H. Health policy and public health implications of obesity in China. Lancet Diabetes Endocrinol. 2021 Jul;9(7):446-461. doi: 10.1016/S2213-8587(21)00118-2. Epub 2021 Jun 4. — View Citation

WHO Guidelines on Physical Activity and Sedentary Behaviour. Geneva: World Health Organization; 2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK566045/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Absolute weight change	Absolute value of weight change from baseline for each group at the 3rd month	3 months (12 weeks)
Other	BMI change	Change in BMI from baseline for each group at the 3rd month. BMI was defined as weight (kg) divided by height squared (m2), weight and height will be combined to report BMI in kg/m^2.	3 months (12 weeks)
Other	Change of waist circumference	Change of waist circumference at the 3rd month	3 months (12 weeks)
Other	Change of waist-to-hip ratio	Change of waist-to-hip ratio at the 3rd month. Waist-to-hip ratio will be defined as waist circumference (cm) to hip circumference (cm).	3 months (12 weeks)
Other	Change of FPG	Change of FPG from baseline	3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)
Other	Change of PPG	Change of PPG from baseline	3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)
Other	Changes of insulin levels	Changes of fasting and oral glucose tolerance test-2h insulin level from baseline	3 months (12 weeks), 6 months (24 weeks), 12 months (48 weeks)
Other	Changes of C-peptide levels	Changes of fasting and oral glucose tolerance test-2h C-peptide levels from baseline	3 months (12 weeks), 6 months (24 weeks), 12 months (48 weeks)
Other	Changes of HbA1c	Changes of HbA1c levels from baseline	3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)
Other	Changes of triglyceride	Changes in triglyceride from baseline	6 months (24 weeks), 12 months (48 weeks)
Other	Changes of total cholesterol	Changes in total cholesterol from baseline	6 months (24 weeks), 12 months (48 weeks)
Other	Changes of LDL-c	Changes in LDL-c from baseline	6 months (24 weeks), 12 months (48 weeks)
Other	Changes of HDL-c	Changes in HDL-c from baseline	6 months (24 weeks), 12 months (48 weeks)
Other	Change of urinary albumin-to-creatinine ratio	Change of urinary albumin-to-creatinine ratio from baseline in each group	6 months (24 weeks), 12 months (48 weeks)
Other	Changes of C-reactive protein	Changes of C-reactive protein in each group relative to baseline	6 months (24 weeks), 12 months (48 weeks)
Primary	Weight change	Proportion of weight change from baseline	3 months (12 weeks)
Secondary	Proportion of =5% weight loss	Proportion of patients who lost at least 5% of their body weight from baseline	3 months (12 weeks)
Secondary	Incident diabetes	New-onset diabetes during follow up	1 month (4 weeks), 2 months (8 weeks), 3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)