History
# Registration date Revision Id
2 2023-05-06, 1402/02/16 268807
1 2022-06-17, 1401/03/27 230175
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  • Protocol summary

    کبد چرب غیر الکلی می تواند منجر به بروز بیماری های قلبی عروقی، بیماری مزمن کلیه و افزایش نرخ مرگ و میر شود. در این مطالعه 60 بیمار در قالب دو گروه، گروه اول تحت درمان با متفورمین طبق دستور و روش استاندارد و در گروه شماره دو، داروی امپاگليفلوزین 25 میلی گرم روزانه به درمان استاندارد اضافه خواهد شد تا تاثیر امپاگليفلوزین روی درمان کبد چرب غیر الکلی بررسی شود.
    کبد چرب غیر الکلی می تواند منجر به بروز بیماری های قلبی عروقی، بیماری مزمن کلیه و افزایش نرخ مرگ و میر شود. در این مطالعه 60 بیمار در قالب دو گروه، گروه اول تحت درمان با متفورمین طبق دستور و روش استاندارد و در گروه شماره دو، داروی امپاگليفلوزین 10 میلی گرم روزانه به درمان استاندارد اضافه خواهد شد تا تاثیر امپاگليفلوزین روی درمان کبد چرب غیر الکلی بررسی شود.
    Patients in the age range of 20-75 years with type 2 diabetes and with HbA1C= 6.5-10% and BMI >20 and weight change of less than 10% in the last three months are indicated for inclusion in this study if only they are treated with metformin 1500 mg daily for at least three months as monotherapy and have a definite diagnosis of NAFLD Excluded patients: Type 1 diabetes, treated with other diabetes drugs except for metformin, Hx pancreatitis, or pancreatic-related diseases, ALT more than twice normal upper limits at baseline and eGFR below 60, decompensated heart failure (FC of 3 and 4), other liver diseases including autoimmune and viral hepatitis, alcohol consumption of more than 140 ccs for women and 250 ccs for men per week, pregnant woman or planning a pregnancy, and breastfeeding.
    Patients in the age range of 20-75 years with type 2 diabetes and with HbA1C= 6.5-10% and BMI >20 and weight change of less than 10% in the last three months are indicated for inclusion in this study if only they are treated with metformin 1500 mg daily for at least three months as monotherapy and have a definite diagnosis of NAFLD Excluded patients: Type 1 diabetes, treated with other diabetes drugs except for metformin, Hx pancreatitis, or pancreatic-related diseases, ALT more than twice normal upper limits at baseline and eGFR below 45, decompensated heart failure (FC of 3 and 4), other liver diseases including autoimmune and viral hepatitis, alcohol consumption of more than 140 ccs for women and 250 ccs for men per week, pregnant woman or planning a pregnancy, and breastfeeding.
    بیماران در بازه سنی 75-20 سال با دیابت نوع دو و با 10- 6/5=HbA1Cو BMI >20 و تغییر وزن کمتر از 10% در سه ماه اخیر، اندیکاسیون ورود به این مطالعه را دارند، با شرط اینکه به مدت حداقل سه ماه به صورت مونوتراپی تحت درمان با متفورمین 1500 میلی گیرم روزانه و در کنار آن تشخیص قطعی NAFLD داشته باشند. بیمارانی که از مطالعه خارج می شوند: دیابت نوع یک، تحت درمان با سایر داروهای دیابت به جز متفورمین در شروع مطالعه، سابقه پانکراتیت یا بیماری های مرتبط با پانكراس، در شروع مطالعه ALT بیشتر از دو برابر نرمال و GFR زیر 60، نارسایی قلب کنترل نشده با تشدید یافته (كلاس 3 و 4)، سایر بیماری های کبدی شامل اوتوایمیون هپاتایتیس و وایرال هپاتایتیس، مصرف الکل بیشتر از 140 سی سی برای خانم و 250 سی سی برای اقایان در هفته، خانم باردار یا کسی که برنامه بارداری دارد، خانم شیرده.
    بیماران در بازه سنی 75-20 سال با دیابت نوع دو و با 10- 6/5=HbA1Cو BMI >20 و تغییر وزن کمتر از 10% در سه ماه اخیر، اندیکاسیون ورود به این مطالعه را دارند، با شرط اینکه به مدت حداقل سه ماه به صورت مونوتراپی تحت درمان با متفورمین 1500 میلی گیرم روزانه و در کنار آن تشخیص قطعی NAFLD داشته باشند. بیمارانی که از مطالعه خارج می شوند: دیابت نوع یک، تحت درمان با سایر داروهای دیابت به جز متفورمین در شروع مطالعه، سابقه پانکراتیت یا بیماری های مرتبط با پانكراس، در شروع مطالعه ALT بیشتر از دو برابر نرمال و GFR زیر 45، نارسایی قلب کنترل نشده با تشدید یافته (كلاس 3 و 4)، سایر بیماری های کبدی شامل اوتوایمیون هپاتایتیس و وایرال هپاتایتیس، مصرف الکل بیشتر از 140 سی سی برای خانم و 250 سی سی برای اقایان در هفته، خانم باردار یا کسی که برنامه بارداری دارد، خانم شیرده.
    Group one is metformin according to the instructions and in group two, 25 mg of empagliflozin once daily will be added to the standard treatment and will be re-evaluated within 6 months. Finally, at the end of the study, they undergo an ultrasound and fiber scan to redefine the liver stage.
    Group one is metformin according to the instructions and in group two, 10 mg of empagliflozin once daily will be added to the standard treatment and will be re-evaluated within 6 months. Finally, at the end of the study, they undergo an ultrasound and fiber scan to redefine the liver stage.
    گروه یک متفورمین طبق دستور گرفته و در گروه دو داروی امپاگليفلوزین 25 میلی گرم صبح ها یک عدد به درمان استاندارد اضافه خواهد شد و در طی 6 ماه مورد بررسی قرار میگیرند. درنهایت در پایان مطالعه تحت سونوگرافی و فیبرواسکن جهت تعیین مجدد استیج کبدی قرار میگیرند.
    گروه یک متفورمین طبق دستور گرفته و در گروه دو داروی امپاگليفلوزین 10 میلی گرم صبح ها یک عدد به درمان استاندارد اضافه خواهد شد و در طی 6 ماه مورد بررسی قرار میگیرند. درنهایت در پایان مطالعه تحت سونوگرافی و فیبرواسکن جهت تعیین مجدد استیج کبدی قرار میگیرند.
  • General information

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    According to the necessity of proper blood sugar control of patients with diabetes (with any grade of NAFLD) with oral anti diabetic medications, and the fact that in diabetes, any grade of NAFLD induced metabolic and cardiovascular complications, even in lower grades of NAFLD, require pharmacological treatment. with considering that in the control group, the patients should be on metformin with dose less than 1500 mg per day before entry to the study, and in the intervention group, the patients must have received a minimum dose of 1500 mg metformin for 3 months before enrollment to the study, therefore, it was not possible for using randomization. In exclusion criteria, GFR was corrected to less than 45 ml/min. Due to the lack of difference between the doses of 10 and 25 mg of empagliflozin in the therapeutic effect on NAFLD in diabetic patients, this drug was started for patients with a dose of 10 mg. The dose of 25 mg recorded in the initial version of the clinical trial was changed to 10 mg/day.
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    با توجه به لزوم کنترل مناسب قند خون بیماران با داروهای خوراکی دیابت(با هر گرید از NAFLD)، و این که در بیماری دیابت ، هر گریدی از NAFLD، تاثیرات متابولیک و کاردیو وسکولار داشته بنابراین حتی گریدهای پایین تر نیز نیاز به مداخله و درمان دارند، همچنین بیماران وارد شده به مطالعه حداقل 3 ماه تحت درمان با متفورمین 1500 میلی گرم در گروه مداخله با امپاگلیفلوزین بوده و همچنین مشاوره تغذیه و تنظیم برنامه فعالیت فیزیکی جهت کنترل وزن صورت گرفته است. لذا در این مرحله در صورت تداوم nafld حتی با گرید یک لزوم دارو درمانی مطرح می باشد. بنابراین کرایتریایی ورود به مطالعه از حداقل گرید 2 nafld به گرید یک کاهش یابد. با توجه به اینکه در گروه کنترل، بیماران قبل ورود به مطالعه باید روی دوز کمتر از 1500 میلی گرم در روز بوده و در گروه مداخله بیماران در بدو ورود به مطالعه باید حداقل دوز 1500 میلی گرم برای 3 ماه دریافت کرده باشند، لذا امکان رندم سازی وجود ندارد. در شرایط خروج از مطالعه GFR به کمتر از 45 ml/min تصحیح گردید. با توجه به عدم تفاوت دوز 10 و 25 میلی گرم امپاگلیفلوزین در نتایج درمانی NAFLDدر دیابت، این دارو برای بیماران با دوز 10 میلیگرم آغاز گردید. دوز 25 میلیگرم ثبت شده در نسخه اولیه مداخله بالینی به 10 میلیگرم اصلاح گردید.
    Controlled type 2 Diabetes Mellitus (T2DM) with HbA1C=6.5-10
    BMI greater than 20, with the last 3 months loss of weight below 10%
    treatment with Metformin, 1500mg daily, at least 3 months as monotherapy
    Statin consumption
    Definitive diagnosis of NAFLD under the supervision of a Gastroenterology subspecialty
    Controlled type 2 Diabetes Mellitus (T2DM) with HbA1C=6.5-10
    BMI greater than 20, with the last 3 months loss of weight below 10%
    treatment with Metformin, 1500mg daily, at least 3 months as monotherapy
    Statin consumption
    Definitive diagnosis of NAFLD under the supervision of a Gastroenterology subspecialty
    at least grade 1 of non-alcoholic fatty liver disease (NAFLD) based on ultrasonography
    دیابت نوع دو و قند خون کنترل شده با 10- 6/5=HbA1C
    BMI بالای 20 و تغییر وزن کمتر از 10% در سه ماه اخیر
    درمان با متفورمین 1500 میلی گیرم روزانه، حداقل سه ماه به صورت مونوتراپی
    مصرف استاتین
    تشخیص قطعی NAFLD تحت نظر فوق تخصص گوارش داشته باشند.
    دیابت نوع دو و قند خون کنترل شده با 10- 6/5=HbA1C
    BMI بالای 20 و تغییر وزن کمتر از 10% در سه ماه اخیر
    درمان با متفورمین 1500 میلی گیرم روزانه، حداقل سه ماه به صورت مونوتراپی
    مصرف استاتین
    تشخیص قطعی NAFLD تحت نظر فوق تخصص گوارش داشته باشند.
    داشتن حداقل گرید 1 کبد چرب بر اساس سونوگرافی
    Type 1 Diabetes Mellitus (T1DM)
    Treated with other diabetes medications except for metformin at baseline
    History of pancreatitis or pancreas related diseases
    At the beginning of the study ALT more than twice normal upper limits
    eGFR lower than 60 ml/min
    Decompensated or untreated Heart Failure (functional class 3 or 4)
    Other liver diseases include autoimmune hepatitis and viral hepatitis
    Alcohol consumption more than 140 cc for women and 250 cc for men per week
    A pregnant woman or someone who is planning a pregnancy
    breastfeeding
    Type 1 Diabetes Mellitus (T1DM)
    Treated with other diabetes medications except for metformin at baseline
    History of pancreatitis or pancreas related diseases
    At the beginning of the study ALT more than twice normal upper limits
    eGFR lower than 45 ml/min
    Decompensated or untreated Heart Failure (functional class 3 or 4)
    Other liver diseases include autoimmune hepatitis and viral hepatitis
    Alcohol consumption more than 140 cc for women and 250 cc for men per week
    A pregnant woman or someone who is planning a pregnancy
    breastfeeding
    دیابت نوع یک
    تحت درمان با سایر داروهای دیابت به جز متفورمین در شروع مطالعه
    سابقه پانکراتیت یا بیماری های مرتبط با پانكراس
    در شروع مطالعه ALT بیشتر از دو برابر نرمال
    eGFR زیر 60
    نارسایی قلب کنترل نشده با تشدید یافته (فانکشنال كلاس 3 و 4)
    سایر بیماری های کبدی شامل هپاتیت اوتوایمیون و هپاتیت ویروسی
    مصرف الکل بیشتر از 140 سی سی برای خانم و 250 سی سی برای اقایان در هفته
    خانم باردار یا کسی که برنامه بارداری دارد
    خانم شیرده
    دیابت نوع یک
    تحت درمان با سایر داروهای دیابت به جز متفورمین در شروع مطالعه
    سابقه پانکراتیت یا بیماری های مرتبط با پانكراس
    در شروع مطالعه ALT بیشتر از دو برابر نرمال
    eGFR زیر 45
    نارسایی قلب کنترل نشده با تشدید یافته (فانکشنال كلاس 3 و 4)
    سایر بیماری های کبدی شامل هپاتیت اوتوایمیون و هپاتیت ویروسی
    مصرف الکل بیشتر از 140 سی سی برای خانم و 250 سی سی برای اقایان در هفته
    خانم باردار یا کسی که برنامه بارداری دارد
    خانم شیرده
  • Sponsors / Funding sources

    #1

    Name of organization / entity - English:
    Name of organization / entity - Persian:
    Full name of responsible person - English: Laya Hooshmand Qarehbagh
    Full name of responsible person - Persian: لعیا هوشمند قره باغ
    Street address - English: Imam Khomeini University Hospital, Ershad St.
    Street address - Persian: مرکز آموزشی درمانی امام خمینی (ره)، خیابان ارشاد
    City - English: Urmia
    City - Persian: ارومیه
    Province: West Azarbaijan
    Country: Iran (Islamic Republic of)
    Postal code: 5715781351
    Phone: +98 44 3346 9931
    Fax:
    Email: laya.hooshmand58@gmail.com
    Web page address:

    Name of organization / entity - English:
    Name of organization / entity - Persian:
    Full name of responsible person - English: Saber Gholizadeh
    Full name of responsible person - Persian: صابر قلی زاده
    Street address - English: Orjhans Street, Resalat Blvd
    Street address - Persian: بلوار رسالت ، کوی اورژانس، ستاد دانشگاه علوم پزشکی ارومیه، معاونت تحقیقات و فناوری
    City - English: Urmia
    City - Persian: ارومیه
    Province: West Azarbaijan
    Country: Iran (Islamic Republic of)
    Postal code: 571478334
    Phone: +98 44 3223 4897
    Fax: +98 44 3222 9059
    Email: sabergholizadeh@yahoo.com
    Web page address:

Protocol summary

Study aim
Assessment of the empagliflozin effect on the non-alcoholic fatty liver of type 2 diabetic patients with metformin-containing regimens
Design
A clinical trial with the parallel control group, an open-label, randomized, phase3, on 60 patients, block randomization was used in SPSS for randomization
Settings and conduct
NAFLD can lead to cardiovascular disease, chronic kidney disease, and increased mortality. In this study, 60 patients in two groups, would be evaluated for the assessment of the empagliflozin effect on the treatment of non-alcoholic fatty liver.
Participants/Inclusion and exclusion criteria
Patients in the age range of 20-75 years with type 2 diabetes and with HbA1C= 6.5-10% and BMI >20 and weight change of less than 10% in the last three months are indicated for inclusion in this study if only they are treated with metformin 1500 mg daily for at least three months as monotherapy and have a definite diagnosis of NAFLD Excluded patients: Type 1 diabetes, treated with other diabetes drugs except for metformin, Hx pancreatitis, or pancreatic-related diseases, ALT more than twice normal upper limits at baseline and eGFR below 45, decompensated heart failure (FC of 3 and 4), other liver diseases including autoimmune and viral hepatitis, alcohol consumption of more than 140 ccs for women and 250 ccs for men per week, pregnant woman or planning a pregnancy, and breastfeeding.
Intervention groups
Group one is metformin according to the instructions and in group two, 10 mg of empagliflozin once daily will be added to the standard treatment and will be re-evaluated within 6 months. Finally, at the end of the study, they undergo an ultrasound and fiber scan to redefine the liver stage.
Main outcome variables
FBS LDL HDL Cholesterol Triglyceride AST ALT ALKP HbA1C CAP score

General information

Reason for update
According to the necessity of proper blood sugar control of patients with diabetes (with any grade of NAFLD) with oral anti diabetic medications, and the fact that in diabetes, any grade of NAFLD induced metabolic and cardiovascular complications, even in lower grades of NAFLD, require pharmacological treatment. with considering that in the control group, the patients should be on metformin with dose less than 1500 mg per day before entry to the study, and in the intervention group, the patients must have received a minimum dose of 1500 mg metformin for 3 months before enrollment to the study, therefore, it was not possible for using randomization. In exclusion criteria, GFR was corrected to less than 45 ml/min. Due to the lack of difference between the doses of 10 and 25 mg of empagliflozin in the therapeutic effect on NAFLD in diabetic patients, this drug was started for patients with a dose of 10 mg. The dose of 25 mg recorded in the initial version of the clinical trial was changed to 10 mg/day.
Acronym
IRCT registration information
IRCT registration number: IRCT20220115053717N1
Registration date: 2022-06-17, 1401/03/27
Registration timing: prospective

Last update: 2023-06-20, 1402/03/30
Update count: 1
Registration date
2022-06-17, 1401/03/27
Registrant information
Name
Reza Pourahmadazar
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 44 3344 1499
Email address
r.poorahmadazar@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2022-06-19, 1401/03/29
Expected recruitment end date
2022-12-19, 1401/09/28
Actual recruitment start date
2022-07-16, 1401/04/25
Actual recruitment end date
2022-10-03, 1401/07/11
Trial completion date
2023-04-05, 1402/01/16
Scientific title
The comparison of the Empagliflozin effect on nonalcoholic fatty liver in patients with diabetic type 2 with metformin-containing regimens
Public title
Investigating the Empagliflozin effect on nonalcoholic fatty liver in patients with diabetic type 2 with metformin-containing regimens
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Controlled type 2 Diabetes Mellitus (T2DM) with HbA1C=6.5-10 BMI greater than 20, with the last 3 months loss of weight below 10% treatment with Metformin, 1500mg daily, at least 3 months as monotherapy Statin consumption Definitive diagnosis of NAFLD under the supervision of a Gastroenterology subspecialty at least grade 1 of non-alcoholic fatty liver disease (NAFLD) based on ultrasonography
Exclusion criteria:
Type 1 Diabetes Mellitus (T1DM) Treated with other diabetes medications except for metformin at baseline History of pancreatitis or pancreas related diseases At the beginning of the study ALT more than twice normal upper limits eGFR lower than 45 ml/min Decompensated or untreated Heart Failure (functional class 3 or 4) Other liver diseases include autoimmune hepatitis and viral hepatitis Alcohol consumption more than 140 cc for women and 250 cc for men per week A pregnant woman or someone who is planning a pregnancy breastfeeding
Age
From 20 years old to 75 years old
Gender
Both
Phase
2-3
Groups that have been masked
No information
Sample size
Target sample size: 60
Actual sample size reached: 60
Randomization (investigator's opinion)
Randomized
Randomization description
Patients will be divided into intervention or control groups using the block randomization method based on generated numbers by Random allocation software. Thus, in this software, first, the number of groups and the total determined sample size will be entered (60 patients), and then in the block section, the Block randomization method will be implemented. Patients will be allocated to groups based on generated numbers. Random Allocation Software version 1.0.0 has been developed by Mr. Saghaei, MD. department of anesthesia, Isfahan University of Medical Sciences, Isfahan, Iran.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Ethics Committees of Urmia University of Medical Sciences
Street address
Orjhans Street, Resalat Blvd, Urmia
City
Urmia
Province
West Azarbaijan
Postal code
571478334
Approval date
2022-01-02, 1400/10/12
Ethics committee reference number
IR.UMSU.HIMAM.REC.1400.010

Health conditions studied

1

Description of health condition studied
Type 2 diabetic patients with nonalcoholic fatty liver disease
ICD-10 code
5A11, DB92
ICD-10 code description
type 2 diabetes mellitus, nonalcoholic fatty liver disease

Primary outcomes

1

Description
CAP score or STAGE determination index of steatohepatitis that is measured and evaluated by Fibroscan
Timepoint
at the beginning and the end of study of(after 6 months of treatment)
Method of measurement
Fibroscan device and its analysis by an experienced unit

Secondary outcomes

empty

Intervention groups

1

Description
Control group: Treatment with metformin according to standard instructions and methods
Category
Treatment - Drugs

2

Description
Intervention group: Treatment with Empagliflozin 25 mg once in the morning added to the standard treatment (Metformin)
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Imam Khomeini University Hospital
Full name of responsible person
Laya Hooshmand Qarehbagh
Street address
Imam Khomeini University Hospital, Ershad St.
City
Urmia
Province
West Azarbaijan
Postal code
5715781351
Phone
+98 44 3346 9931
Email
laya.hooshmand58@gmail.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Oroumia University of Medical Sciences
Full name of responsible person
Saber Gholizadeh
Street address
Orjhans Street, Resalat Blvd
City
Urmia
Province
West Azarbaijan
Postal code
571478334
Phone
+98 44 3223 4897
Fax
+98 44 3222 9059
Email
sabergholizadeh@yahoo.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Oroumia University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic

Person responsible for general inquiries

Contact
Name of organization / entity
Oroumia University of Medical Sciences
Full name of responsible person
Laya Hooshmand Qarehbagh
Position
Associate professor
Latest degree
Subspecialist
Other areas of specialty/work
Internal Medicine
Street address
Imam Khomeini University Hospital, Ershad St.
City
Urmia
Province
West Azarbaijan
Postal code
5715781351
Phone
+98 44 3346 9931
Email
laya.hooshmand58@gmail.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Oroumia University of Medical Sciences
Full name of responsible person
Laya Hooshmand Qarehbagh
Position
Associate professor
Latest degree
Subspecialist
Other areas of specialty/work
Internal Medicine
Street address
Imam Khomeini University Hospital, Ershad St.
City
Urmia
Province
West Azarbaijan
Postal code
5715781351
Phone
+98 44 3346 9931
Email
laya.hooshmand58@gmail.com

Person responsible for updating data

Contact
Name of organization / entity
Oroumia University of Medical Sciences
Full name of responsible person
Laya Hooshmand Qarehbagh
Position
Associate professor
Latest degree
Subspecialist
Other areas of specialty/work
Internal Medicine
Street address
Imam Khomeini University Hospital, Ershad St.
City
Urmia
Province
West Azarbaijan
Postal code
5715781351
Phone
+98 44 3346 9931
Email
laya.hooshmand58@gmail.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
No - There is not a plan to make this available
Statistical Analysis Plan
No - There is not a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Not applicable
Data Dictionary
Not applicable
Title and more details about the data/document
The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
When the data will become available and for how long
The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
To whom data/document is available
The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
Under which criteria data/document could be used
The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
From where data/document is obtainable
The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
What processes are involved for a request to access data/document
The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
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