Clinical trial NCT06216340: Efficacy of Henagliflozin for Weight Loss in Obesity Without Diabetes
Official title: Efficacy of Henagliflozin for Weight Loss in Obesity Without Diabetes: a Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Obese
Weight Loss
Pre-diabetes
Keywords: Henagliflozin
Obese
Weight loss
Glucose
Lead sponsor: The First People's Hospital of Changzhou
Sponsor class: OTHER
Collaborators: name: The Second Hospital of Nanjing Medical University
name: The First Affiliated Hospital of Soochow University
name: Second Affiliated Hospital of Soochow University
name: Wuxi People's Hospital
name: Northern Jiangsu People's Hospital
name: The Affiliated Hospital of Xuzhou Medical University
name: The First People's Hospital of Lianyungang
name: Affiliated Hospital of Jiangsu University
name: The fourth affiliated hospital of nantong university
First posted: 2024-01-22
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are randomly divided into two groups: control group and intervention group. In control group, Placebo and diet-exercise therapy is used. In intervention group, 10mg of henagliflozin and diet-exercise therapy is used.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Weight change
timeFrame: 3 months (12 weeks)
Secondary outcomes:
measure: Proportion of ≥5% weight loss
timeFrame: 3 months (12 weeks)
measure: Incident diabetes
timeFrame: 1 month (4 weeks), 2 months (8 weeks), 3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)
Other outcomes:
measure: Absolute weight change
timeFrame: 3 months (12 weeks)
measure: BMI change
timeFrame: 3 months (12 weeks)
measure: Change of waist circumference
timeFrame: 3 months (12 weeks)
measure: Change of waist-to-hip ratio
timeFrame: 3 months (12 weeks)
measure: Change of FPG
timeFrame: 3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)
measure: Change of PPG
timeFrame: 3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)
measure: Changes of insulin levels
timeFrame: 3 months (12 weeks), 6 months (24 weeks), 12 months (48 weeks)
measure: Changes of C-peptide levels
timeFrame: 3 months (12 weeks), 6 months (24 weeks), 12 months (48 weeks)
measure: Changes of HbA1c
timeFrame: 3 months (12 weeks), 6 months (24 weeks), 9 months (36 weeks), 12 months (48 weeks)
measure: Changes of triglyceride
timeFrame: 6 months (24 weeks), 12 months (48 weeks)
measure: Changes of total cholesterol
timeFrame: 6 months (24 weeks), 12 months (48 weeks)
measure: Changes of LDL-c
timeFrame: 6 months (24 weeks), 12 months (48 weeks)
measure: Changes of HDL-c
timeFrame: 6 months (24 weeks), 12 months (48 weeks)
measure: Change of urinary albumin-to-creatinine ratio
timeFrame: 6 months (24 weeks), 12 months (48 weeks)
measure: Changes of C-reactive protein
timeFrame: 6 months (24 weeks), 12 months (48 weeks)
Locations:
Study officials:
affiliation: Affiliated Hospital of Jiangsu University
name: Ling Yang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nanjing Medical University
name: Yu Liu, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: First affiliated hospital of soochow university
name: Bimin Shi, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital of Soochow University
name: Ji Hu
role: PRINCIPAL_INVESTIGATOR
affiliation: Wuxi People's Hospital
name: Xiaowei Zhu, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northern Jiangsu People's Hospital
name: Zhenwen Zhang, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Hospital of Xuzhou Medical University
name: Hongwei Ling, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First People's Hospital of Lianyungang
name: Ning Xu, Bachelor
role: PRINCIPAL_INVESTIGATOR
affiliation: YANCHENG NO.1 PEOPLE'S HOSPITAL
name: Yanmei Liu, MD
role: PRINCIPAL_INVESTIGATOR
References:
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