Protocol summary
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Study aim
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Assessment of the empagliflozin effect on the non-alcoholic fatty liver of type 2 diabetic patients with metformin-containing regimens
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Design
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A clinical trial with the parallel control group, an open-label, randomized, phase3, on 60 patients, block randomization was used in SPSS for randomization
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Settings and conduct
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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.
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Participants/Inclusion and exclusion criteria
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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.
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Intervention groups
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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.
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Main outcome variables
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FBS
LDL
HDL
Cholesterol
Triglyceride
AST
ALT
ALKP
HbA1C
CAP score
General information
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Reason for update
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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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Acronym
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IRCT registration information
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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
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Registration date
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2022-06-17, 1401/03/27
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2022-06-19, 1401/03/29
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Expected recruitment end date
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2022-12-19, 1401/09/28
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Actual recruitment start date
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2022-07-16, 1401/04/25
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Actual recruitment end date
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2022-10-03, 1401/07/11
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Trial completion date
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2023-04-05, 1402/01/16
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Scientific title
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The comparison of the Empagliflozin effect on nonalcoholic fatty liver in patients with diabetic type 2 with metformin-containing regimens
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Public title
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Investigating the Empagliflozin effect on nonalcoholic fatty liver in patients with diabetic type 2 with metformin-containing regimens
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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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
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Age
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From 20 years old to 75 years old
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Gender
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Both
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Phase
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2-3
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Groups that have been masked
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No information
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Sample size
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Target sample size:
60
Actual sample size reached:
60
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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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.
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Blinding (investigator's opinion)
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Not blinded
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Blinding description
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2022-01-02, 1400/10/12
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Ethics committee reference number
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IR.UMSU.HIMAM.REC.1400.010
Health conditions studied
1
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Description of health condition studied
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Type 2 diabetic patients with nonalcoholic fatty liver disease
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ICD-10 code
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5A11, DB92
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ICD-10 code description
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type 2 diabetes mellitus, nonalcoholic fatty liver disease
Primary outcomes
1
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Description
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CAP score or STAGE determination index of steatohepatitis that is measured and evaluated by Fibroscan
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Timepoint
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at the beginning and the end of study of(after 6 months of treatment)
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Method of measurement
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Fibroscan device and its analysis by an experienced unit
Intervention groups
1
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Description
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Control group: Treatment with metformin according to standard instructions and methods
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Category
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Treatment - Drugs
2
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Description
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Intervention group: Treatment with Empagliflozin 25 mg once in the morning added to the standard treatment (Metformin)
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Oroumia University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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No - There is not a plan to make this available
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Statistical Analysis Plan
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No - There is not a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Not applicable
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Data Dictionary
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Not applicable
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Title and more details about the data/document
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The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
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When the data will become available and for how long
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The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
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To whom data/document is available
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The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
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Under which criteria data/document could be used
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The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
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From where data/document is obtainable
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The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
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What processes are involved for a request to access data/document
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The data that support the findings of this study are available from the corresponding author, L. H., upon reasonable request.
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Comments
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