ChiCTR2400089293 版本V1.0 版本创建时间2024/09/05 10:31:58 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2400089293 

最近更新日期：

Date of Last Refreshed on：

2024-09-05 10:31:53 

注册时间：

Date of Registration：

2024-09-05 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

Effect of Sodium Glucose Co-transporter 2 (SGLT2) inhibitor on reducing atypical antipsychotics-induced weight gain in schizophrenia spectrum disorder – A Randomized Controlled Trial

Public title：

Effect of Sodium Glucose Co-transporter 2 (SGLT2) inhibitor on reducing atypical antipsychotics-induced weight gain in schizophrenia spectrum disorder – A Randomized Controlled Trial

注册题目简写：

English Acronym：

研究课题的正式科学名称：

Effect of Sodium Glucose Co-transporter 2 (SGLT2) inhibitor on reducing atypical antipsychotics-induced weight gain in schizophrenia spectrum disorder – A Randomized Controlled Trial

Scientific title：

Effect of Sodium Glucose Co-transporter 2 (SGLT2) inhibitor on reducing atypical antipsychotics-induced weight gain in schizophrenia spectrum disorder – A Randomized Controlled Trial

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

Wong Sin Ying 

研究负责人：

Wong Sin Ying 

Applicant：

Wong Sin Ying 

Study leader：

Wong Sin YIng 

申请注册联系人电话：

Applicant telephone：

+852 9335 2329

研究负责人电话：

Study leader's telephone：

+852 9335 2329

申请注册联系人传真 ：

Applicant Fax：

wsy775@ha.org.hk

研究负责人传真：

Study leader's fax：

wsy775@ha.org.hk

申请注册联系人电子邮件：

Applicant E-mail：

wsy775@ha.org.hk

研究负责人电子邮件：

Study leader's E-mail：

wsy775@ha.org.hk

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

Department of Psychiatry, Tai Po Hospital, 9 Chuen On Road, New Territories, Hong Kong, China

研究负责人通讯地址：

Department of Psychiatry, Tai Po Hospital, 9 Chuen On Road, New Territories, Hong Kong, China

Applicant address：

Department of Psychiatry, Tai Po Hospital, 9 Chuen On Road, New Territories, Hong Kong, China

Study leader's address：

Department of Psychiatry, Tai Po Hospital, 9 Chuen On Road, New Territories, Hong Kong, China

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

Tai Po Hospital

Applicant's institution：

Tai Po Hospital

研究负责人所在单位：

Tai Po Hospital

Affiliation of the Leader：

Tai Po Hospital

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

2023.256-T

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee

Name of the ethic committee：

Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

2023-07-14 00:00:00

伦理委员会联系人：

Envy Lee

Contact Name of the ethic committee：

Envy Lee

伦理委员会联系地址：

8/F, Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong, China

Contact Address of the ethic committee：

8/F, Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+852 3503 3935

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

Tai Po Hospital

Primary sponsor：

Tai Po Hospital

研究实施负责（组长）单位地址：

9 Chuen On Road, Tai Po, New Territories, Hong Kong, China

Primary sponsor's address：

9 Chuen On Road, Tai Po, New Territories, Hong Kong, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

not applicable

省(直辖市)：

not applicable

市(区县)：

Country：

not applicable

Province：

not applicable

City：

单位(医院)：

not applicable

具体地址：

not applicable

Institution
hospital：

not applicable

Address：

not applicable

经费或物资来源：

Not applicable; there is no funding

Source(s) of funding：

Not applicable; there is no funding

Target disease：

Schizophrenia spectrum disorder

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 II期临床试验 

Study phase：

2

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

The primary objective of the study is to evaluate the effect of the combination of SGLT2 inhibitor and lifestyle intervention on weight in patients suffering from schizophrenia spectrum disorder on atypical antipsychotics, compared to the combination of placebo and lifestyle intervention. The secondary objectives of the study include: (i) To evaluate the effect of SGLT2 inhibitor on improving the metabolic traits in patients with schizophrenia spectrum disorder who is taking atypical antipsychotics, compared to the placebo group receiving the same lifestyle intervention. (ii) To compare the safety profile and incidence of adverse events between SGLT2 inhibitor and placebo in patients suffering from schizophrenia spectrum disorder on atypical antipsychotics.  

Objectives of Study：

The primary objective of the study is to evaluate the effect of the combination of SGLT2 inhibitor and lifestyle intervention on weight in patients suffering from schizophrenia spectrum disorder on atypical antipsychotics, compared to the combination of placebo and lifestyle intervention. The secondary objectives of the study include: (i) To evaluate the effect of SGLT2 inhibitor on improving the metabolic traits in patients with schizophrenia spectrum disorder who is taking atypical antipsychotics, compared to the placebo group receiving the same lifestyle intervention. (ii) To compare the safety profile and incidence of adverse events between SGLT2 inhibitor and placebo in patients suffering from schizophrenia spectrum disorder on atypical antipsychotics.

药物成份或治疗方案详述：

Atypical antipsychotics have been increasingly used for the management of patients with a variety of psychiatric disorders. However, there has been a growing concern that the use of atypical antipsychotics may be related to potentially serious adverse metabolic effects, including weight gain, dyslipidemia, and glucose intolerance. These adverse effects, especially weight gain, not only influence adherence with drug treatment but are also associated with substantial medical morbidity and mortality. When antipsychotic-induced weight gain happens, the recommended initial options are switching to a relatively weight-neutral antipsychotics or instituting lifestyle intervention (or both). However, these are often difficult as switching always carries a risk of relapse, whereas many patients with schizophrenia spectrum disorder have been suffering from negative symptoms making them difficult to perform or sustain lifestyle interventions. Various medications have been reported to counteract antipsychotic-induced weight gain effectively, especially anti-diabetic drugs like metformin and liraglutide. Nevertheless, their clinical implementation has been limited due to various reasons, including the heterogenicity of studies, modest effect, need of twice-daily dosing, possible gastrointestinal side-effect and subcutaneous injection delivery method. Sodium-glucose transporter 2 (SGLT2) inhibitors are a novel class of oral anti-diabetic drug approved for treatment of Type 2 diabetes mellitus by the Food and Drug Administration (FDA). By inhibiting the SGLT2 in the renal proximal convoluted tubule, it causes net caloric loss via decreasing the renal threshold for glucose excretion and increasing urinary glucose excretion. As a result, it improves glycaemic control and lowers body weight. Such effect is observable in both diabetic and non-diabetic patients. Large clinical trials with SGLT2 inhibitors also demonstrated their ability to improve morbidity and reduce mortality, and suggested their cardioprotective, nephroprotective and neuroprotective properties, with benefits even in patients without diabetes. Its daily-dosing frequency has also made it particularly attractive. To our knowledge, there has not been any double-blind, placebo-controlled studies directly comparing lifestyle intervention alone with its combination of SGLT2 inhibitors for antipsychotic-induced weight gain among patients with schizophrenia spectrum disorder. The proposed study will be a 16-week randomized, double-blind, placebo-controlled trial that tested the efficacy of lifestyle intervention alone and in combination of SGLT2 inhibitors to reduce weight gain induced by antipsychotics in patients with schizophrenia spectrum disorder. Adults with diagnosis of schizophrenia spectrum disorder will be recruited from regional psychiatric outpatient clinics and psychiatric day hospitals. Participants will be randomized into either the SGLT2 group or the placebo group. Both groups will then be followed at regular intervals for assessment on their weight and metabolic traits.  

Description for medicine or protocol of treatment in detail：

Atypical antipsychotics have been increasingly used for the management of patients with a variety of psychiatric disorders. However, there has been a growing concern that the use of atypical antipsychotics may be related to potentially serious adverse metabolic effects, including weight gain, dyslipidemia, and glucose intolerance. These adverse effects, especially weight gain, not only influence adherence with drug treatment but are also associated with substantial medical morbidity and mortality. When antipsychotic-induced weight gain happens, the recommended initial options are switching to a relatively weight-neutral antipsychotics or instituting lifestyle intervention (or both). However, these are often difficult as switching always carries a risk of relapse, whereas many patients with schizophrenia spectrum disorder have been suffering from negative symptoms making them difficult to perform or sustain lifestyle interventions. Various medications have been reported to counteract antipsychotic-induced weight gain effectively, especially anti-diabetic drugs like metformin and liraglutide. Nevertheless, their clinical implementation has been limited due to various reasons, including the heterogenicity of studies, modest effect, need of twice-daily dosing, possible gastrointestinal side-effect and subcutaneous injection delivery method. Sodium-glucose transporter 2 (SGLT2) inhibitors are a novel class of oral anti-diabetic drug approved for treatment of Type 2 diabetes mellitus by the Food and Drug Administration (FDA). By inhibiting the SGLT2 in the renal proximal convoluted tubule, it causes net caloric loss via decreasing the renal threshold for glucose excretion and increasing urinary glucose excretion. As a result, it improves glycaemic control and lowers body weight. Such effect is observable in both diabetic and non-diabetic patients. Large clinical trials with SGLT2 inhibitors also demonstrated their ability to improve morbidity and reduce mortality, and suggested their cardioprotective, nephroprotective and neuroprotective properties, with benefits even in patients without diabetes. Its daily-dosing frequency has also made it particularly attractive. To our knowledge, there has not been any double-blind, placebo-controlled studies directly comparing lifestyle intervention alone with its combination of SGLT2 inhibitors for antipsychotic-induced weight gain among patients with schizophrenia spectrum disorder. The proposed study will be a 16-week randomized, double-blind, placebo-controlled trial that tested the efficacy of lifestyle intervention alone and in combination of SGLT2 inhibitors to reduce weight gain induced by antipsychotics in patients with schizophrenia spectrum disorder. Adults with diagnosis of schizophrenia spectrum disorder will be recruited from regional psychiatric outpatient clinics and psychiatric day hospitals. Participants will be randomized into either the SGLT2 group or the placebo group. Both groups will then be followed at regular intervals for assessment on their weight and metabolic traits.  

纳入标准：

1) Who are 18-64 years old; 2) Who met criteria for schizophrenia spectrum and other psychotic disorders on Chinese-bilingual Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I, patient version (SCID-I) except for substance/medication-induced psychotic disorder, psychotic disorder due to another medical condition, catatonia associated with another mental disorder, catatonic disorder due to another medical condition, and unspecified catatonia; 3) Who are receiving at least one of the targeted atypical antipsychotics -- clozapine, olanzapine, quetiapine, risperidone or paliperidone, for 6 months with its dosage and concomitant psychiatric medications not changed over the past 1 month prior to study entry; 4) Who are Asians with Body Mass Index (BMI) ≥ 23 kg/m2 (Classified as overweight or obese according to World Health Organization (WHO)’s classification for Asia-Pacific); 5) Who are able to understand spoken instructions in Cantonese and are able to read traditional Chinese; 6) Being clinically stable as assessed by their treating psychiatrist and having a Clinical Global Impressions scale severity rating (CGI-S) ≤4 (moderately ill) 7) Who are able to give informed consent.

Inclusion criteria

1) Who are 18-64 years old; 2) Who met criteria for schizophrenia spectrum and other psychotic disorders on Chinese-bilingual Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I, patient version (SCID-I) except for substance/medication-induced psychotic disorder, psychotic disorder due to another medical condition, catatonia associated with another mental disorder, catatonic disorder due to another medical condition, and unspecified catatonia; 3) Who are receiving at least one of the targeted atypical antipsychotics -- clozapine, olanzapine, quetiapine, risperidone or paliperidone, for 6 months with its dosage and concomitant psychiatric medications not changed over the past 1 month prior to study entry; 4) Who are Asians with Body Mass Index (BMI) ≥ 23 kg/m2 (Classified as overweight or obese according to World Health Organization (WHO)’s classification for Asia-Pacific); 5) Who are able to understand spoken instructions in Cantonese and are able to read traditional Chinese; 6) Being clinically stable as assessed by their treating psychiatrist and having a Clinical Global Impressions scale severity rating (CGI-S) ≤4 (moderately ill) 7) Who are able to give informed consent.

排除标准：

1) Who had received a psychiatric diagnosis other than schizophrenia spectrum disorder as confirmed by SCID-I, had learning disability or had any active substance abuse or dependence for the past six months (except for nicotine); 2) With evidence of active liver, thyroid or renal dysfunction, cardiovascular disease, uncontrolled hypertension, diabetes mellitus or malignancy, defined as: i. Liver dysfunction: liver transaminases >3 times upper normal limit; ii. Renal dysfunction: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2; iii. Cardiovascular disease: decompensated heart failure (New York Heart Association (NYHA) class III or IV), unstable angina pectoris and/ or myocardial infarction within the last 12 months; iv. Uncontrolled hypertension: systolic blood pressure >180mmHg or diastolic blood pressure >100 mmHg; v. Diabetes mellitus: HbA1c >6.4% (conventional unit). 3) Who had used any medication for weight loss within the preceding month prior to study entry; 4) Who are having treatment with oral corticosteroids; 5) Suffering from recurrent genitourinary infection, defined as ≥2 infections in past six months or ≥3 infections in the past year; 6) Who are in pregnancy or lactation within recent 3 years.

Exclusion criteria：

1) Who had received a psychiatric diagnosis other than schizophrenia spectrum disorder as confirmed by SCID-I, had learning disability or had any active substance abuse or dependence for the past six months (except for nicotine); 2) With evidence of active liver, thyroid or renal dysfunction, cardiovascular disease, uncontrolled hypertension, diabetes mellitus or malignancy, defined as: i. Liver dysfunction: liver transaminases >3 times upper normal limit; ii. Renal dysfunction: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2; iii. Cardiovascular disease: decompensated heart failure (New York Heart Association (NYHA) class III or IV), unstable angina pectoris and/ or myocardial infarction within the last 12 months; iv. Uncontrolled hypertension: systolic blood pressure >180mmHg or diastolic blood pressure >100 mmHg; v. Diabetes mellitus: HbA1c >6.4% (conventional unit). 3) Who had used any medication for weight loss within the preceding month prior to study entry; 4) Who are having treatment with oral corticosteroids; 5) Suffering from recurrent genitourinary infection, defined as ≥2 infections in past six months or ≥3 infections in the past year; 6) Who are in pregnancy or lactation within recent 3 years.

研究实施时间：

Study execute time：

从 From 2023-11-17 00:00:00至 To 2024-09-30 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2023-11-24 00:00:00 至 To 2024-06-30 00:00:00  

干预措施：

Interventions：

组别：

SGLT2 inhibitor group

样本量：

26

Group：

SGLT2 inhibitor group

Sample size：

干预措施：

Empagliflozin 10mg daily with lifestyle intervention

干预措施代码：

Intervention：

Empagliflozin 10mg daily with lifestyle intervention

Intervention code：

组别：

Placebo group

样本量：

26

Group：

Placebo group

Sample size：

干预措施：

Placebo with lifestyle intervention

干预措施代码：

Intervention：

Placebo with lifestyle intervention

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 China

省(直辖市)：

 Hong Kong 

市(区县)：

  

Country：

China  

Province：

Hong Kong 

City：

 

单位(医院)：

Tai Po Hospital 

单位级别：

Psychiatric Day Hospital  

Institution
hospital：

Tai Po Hospital

Level of the institution：

Psychiatric Day Hospital

国家：

 China

省(直辖市)：

 Hong Kong 

市(区县)：

  

Country：

China 

Province：

Hong Kong 

City：

 

单位(医院)：

Alice Ho Miu Ling Nethersole Hospital  

单位级别：

Psychiatric outpatient clinic  

Institution
hospital：

Alice Ho Miu Ling Nethersole Hospital

Level of the institution：

Psychiatric outpatient clinic

国家：

 China

省(直辖市)：

 Hong Kong 

市(区县)：

  

Country：

China 

Province：

Hong Kong 

City：

 

单位(医院)：

North District Hospital 

单位级别：

Psychiatric outpatient clinic  

Institution
hospital：

North District Hospital

Level of the institution：

Psychiatric outpatient clinic

国家：

 China

省(直辖市)：

 Hong Kong 

市(区县)：

  

Country：

China 

Province：

Hong Kong 

City：

 

单位(医院)：

Prince of Wales Hospital 

单位级别：

Psychiatric outpatient clinic 

Institution
hospital：

Prince of Wales Hospital

Level of the institution：

Psychiatric outpatient clinic

国家：

 China

省(直辖市)：

 Hong Kong 

市(区县)：

  

Country：

China 

Province：

Hong Kong 

City：

 

单位(医院)：

Shatin Hospital 

单位级别：

Psychiatric day hospital 

Institution
hospital：

Shatin Hospital

Level of the institution：

Psychiatric day hospital

测量指标：

Outcomes：

指标中文名：

Body weight (kg)

指标类型：

主要指标

Outcome：

Body weight (kg)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

Body Mass Index (BMI)(kg/m2)

指标类型：

主要指标

Outcome：

Body Mass Index (BMI)(kg/m2)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

Waist circumference (cm)

指标类型：

次要指标

Outcome：

Waist circumference (cm)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

Low-density lipoprotein (LDL) (mmol/L)

指标类型：

次要指标

Outcome：

Low-density lipoprotein (LDL) (mmol/L)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

High-density lipoprotein (HDL) (mmol/L)

指标类型：

次要指标

Outcome：

High-density lipoprotein (HDL) (mmol/L)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

Total triglycerides (TG) (mmol/L)

指标类型：

次要指标

Outcome：

Total triglycerides (TG) (mmol/L)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

Blood pressure (mmHg)

指标类型：

次要指标

Outcome：

Blood pressure (mmHg)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

HbA1c (mmol/mol)

指标类型：

次要指标

Outcome：

HbA1c (mmol/mol)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

Fasting glucose (mmol/L)

指标类型：

次要指标

Outcome：

Fasting glucose (mmol/L)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

Incidence of adverse events

指标类型：

副作用指标

Outcome：

Incidence of adverse events

Type：

Adverse events

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

Blood

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

结束

/Completed

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 64 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

The subjects will be randomly allocated to the SGLT2 inhibitor group or the placebo group by a block randomization procedure with 1:1 group allocation. Allocation concealment will be adopted to prevent selection bias. The randomization sequence will be electronically generated, and conducted independently of the study psychiatrist in separate facility by helper.

Randomization Procedure (please state who generates the random number sequence and by what method)：

The subjects will be randomly allocated to the SGLT2 inhibitor group or the placebo group by a block randomization procedure with 1:1 group allocation. Allocation concealment will be adopted to prevent selection bias. The randomization sequence will be electronically generated, and conducted independently of the study psychiatrist in separate facility by helper.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

Both the assessor and the subjects will be blinded to the procedure. All subjects will not be informed of the group allocation during the study, and they will be assessed by the study psychiatrist who is blinded to the group allocation. Both placebo and empagliflozin will be matched in size and appearance. Unblinding will be performed whenever needed for safety reasons.

Blinding：

Both the assessor and the subjects will be blinded to the procedure. All subjects will not be informed of the group allocation during the study, and they will be assessed by the study psychiatrist who is blinded to the group allocation. Both placebo and empagliflozin will be matched in size and appearance. Unblinding will be performed whenever needed for safety reasons.

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

Yes

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

On Individual request.

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

On Individual request

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

Raw data and electronic data will be stored in locked space and password protected computers respectively. All data will be destroyed 5 years after completion of study and submission for publication. Only investigators of the study will have access to the personal and study data during and after the study. The principal investigator will be responsible for safekeeping the data.

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Raw data and electronic data will be stored in locked space and password protected computers respectively. All data will be destroyed 5 years after completion of study and submission for publication. Only investigators of the study will have access to the personal and study data during and after the study. The principal investigator will be responsible for safekeeping the data.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2024-09-05 10:31:53