Protocol summary
-
Study aim
-
Comparing the Empagliflozin with Pioglitazone effect on nonalcoholic fatty liver in diabetic type 2 patients treated with metformin
-
Design
-
An open-label, randomized clinical trial study with parallel groups and phases 3 on 60 patients. Randomization will be done with the block randomization method using Random allocation software.
-
Settings and conduct
-
This open-label, randomized clinical trial study will be conducted on 60 patients of type 2 diabetics and at least grade 1 of non-alcoholic fatty liver disease in Urmia Imam Khomeini Hospital.
-
Participants/Inclusion and exclusion criteria
-
In this study, 60 patients treated with metformin for at least three months with a minimum dose of 1500 mg daily and with at least grade 1 non-alcoholic fatty liver will be included. The main exclusion criteria included patients receiving drugs that stimulate insulin secretion, or insulin, type 1 diabetes, patients treated with diabetes drugs including sitagliptin and liraglutide, and other liver diseases including autoimmune hepatitis and viral hepatitis.
-
Intervention groups
-
In group one, patients will receive 30 mg pioglitazone daily, and in group two, 10 mg empagliflozin daily in addition to the standard treatment (metformin) for 6 months. If Hb A1c is not controlled after three months of intervention, the dose of metformin will be increased from 1500 to 2500 and the dose of empagliflozin will be increased from 10 to 25 mg. Patients who will not take at least 80% of the tablets during the study will be excluded.
-
Main outcome variables
-
liver steatosis score; Liver enzymes including Alanine transaminase (ALT); Aspartate transaminase (AST); Alkaline phosphatase (ALKP).
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.
Also, the patients included in the current study have been treated with metformin 1500 mg for at least 3 months, and nutrition counseling and physical activity program adjustment have been done to control weight. Therefore, if subjects still have grade 1 NAFLD, adding new agents for therapy is necessary. Hence, the inclusion criteria for the study should be change from the minimum grade 2 NAFLD to grade 1.
According to the time of receiving the study ethics code on 14.7.2022, sampling has started after that date. Therefore, it is requested to change the sampling start time to 20.3.2023
-
Acronym
-
-
IRCT registration information
-
IRCT registration number:
IRCT20220928056051N1
Registration date:
2022-10-04, 1401/07/12
Registration timing:
retrospective
Last update:
2023-04-23, 1402/02/03
Update count:
1
-
Registration date
-
2022-10-04, 1401/07/12
-
Registrant information
-
-
Recruitment status
-
Recruitment complete
-
Funding source
-
-
Expected recruitment start date
-
2022-07-14, 1401/04/23
-
Expected recruitment end date
-
2023-03-20, 1401/12/29
-
Actual recruitment start date
-
2022-07-16, 1401/04/25
-
Actual recruitment end date
-
2022-09-26, 1401/07/04
-
Trial completion date
-
2023-04-05, 1402/01/16
-
Scientific title
-
Comparing the effect of Empagliflozin with Pioglitazone on nonalcoholic fatty liver in diabetic type 2 patients treated with metformin
-
Public title
-
Comparing the effect of Empagliflozin with Pioglitazone on nonalcoholic fatty liver
-
Purpose
-
Treatment
-
Inclusion/Exclusion criteria
-
Inclusion criteria:
Age between 20 to 75 years
Type 2 diabetes
A hemoglobin A1C (HbA1c) between 7 and 10
Body mass index (BMI) between 20 to 40 kg/m2
Treated with metformin for at least three months with a minimum dose of 1500 mg daily
َAt least grade 1 of non-alcoholic fatty liver disease (NAFLD)
Exclusion criteria:
Patients receiving drugs that stimulate insulin secretion, or insulin
Type 1 diabetes
Patients treated with diabetes drugs including sitagliptin and liraglutide
Glomerular Filtration Rate (GFR) less than 30
Uncontrolled or aggravated heart disease (class 3 and 4)
Liver diseases including autoimmune hepatitis and viral hepatitis
Alcohol consumption of more than 140 cc for women and 250 cc for men per week
Pregnancy
breastfeeding
History of recurrent urinary tract infection
Bladder Cancer
-
Age
-
From 20 years old to 75 years old
-
Gender
-
Both
-
Phase
-
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 two 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, and then in the block section, the Block randomization method will be implemented. According to the total sample size (60 patients), 15 blocks of 4 will be used. Patients will be allocated to intervention groups based on generated numbers.
-
Blinding (investigator's opinion)
-
Not blinded
-
Blinding description
-
-
Placebo
-
Not used
-
Assignment
-
Parallel
-
Other design features
-
Ethics committees
1
-
Ethics committee
-
-
Approval date
-
2022-07-13, 1401/04/22
-
Ethics committee reference number
-
IR.UMSU.REC.1401.180
Health conditions studied
1
-
Description of health condition studied
-
Non-alcoholic fatty liver disease
-
ICD-10 code
-
K76.0
-
ICD-10 code description
-
Fatty (change of) liver, not elsewhere classified
Primary outcomes
1
-
Description
-
Liver steatosis score
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
Fibroscan
2
-
Description
-
Alanine transaminase (ALT)
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
blood sample
3
-
Description
-
Aspartate transaminase (AST)
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
blood sample
4
-
Description
-
Alkaline phosphatase (ALKP)
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
blood sample
Secondary outcomes
1
-
Description
-
HbA۱c
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
Blood sample
2
-
Description
-
Cholesterol
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
Blood sample
3
-
Description
-
high-density lipoprotein (HDL)
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
Blood sample
4
-
Description
-
low-density lipoprotein (LDL)
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
Blood sample
5
-
Description
-
triglyceride
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
Blood sample
6
-
Description
-
Serum creatinine
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
Blood sample
7
-
Description
-
Glomerular filtration rate (GFR)
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
Based on the formula
8
-
Description
-
Serum insulin
-
Timepoint
-
Before and 6 months after the intervention
-
Method of measurement
-
Blood sample
Intervention groups
1
-
Description
-
Intervention group: In group one, patients will receive 30 mg pioglitazone daily in addition to the standard treatment (metformin) for 6 months.
-
Category
-
Treatment - Drugs
2
-
Description
-
Intervention group: in group two, patients will receive 10 mg empagliflozin daily in addition to the standard treatment (metformin) for 6 months.
-
Category
-
Treatment - Drugs
1
-
Sponsor
-
-
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
Sharing plan
-
Deidentified Individual Participant Data Set (IPD)
-
No - There is not a plan to make this available
-
Justification/reason for indecision/not sharing IPD
-
Confidentiality of patient information
-
Study Protocol
-
No - There is not a plan to make this available
-
Statistical Analysis Plan
-
Not applicable
-
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
-
Individual data will not be published and the results will be accessible as a published article.
-
When the data will become available and for how long
-
After publishing the article
-
To whom data/document is available
-
Researchers
-
Under which criteria data/document could be used
-
Not applicable
-
From where data/document is obtainable
-
address of the corresponding author: hooshmand.l@umsu.ac.ir
-
What processes are involved for a request to access data/document
-
address of the corresponding author: hooshmand.l@umsu.ac.ir
-
Comments
-