Protocol summary

Study aim
Comparison of metformin alone and combination of metformin with ezetimibe on PPAR-γ and adiponectin gene expression ,serum level of medical enzymes , degree of dietary steatosis , glycemic and blood lipid parameters in non- alcoholic fatty liver disease in grade 2 patients
Design
Clinical trial with 2 control and intervention groups, parallel groups, randomized, phase 4 on two groups of 80 people.
Settings and conduct
The participants in this project will be entered by the endocrinology and metabolism specialist from Nikbakht Clinic in Isfahan in 2023 based on the entry criteria of the study. Serum lipid profile (HDL and LDL-Cholesterol, Triglycerides) using commercial enzymatic method, serum level of GGT, AST and ALT by calorimetric method, insulin level by Cobas e411device, and interleukin 6 level by Imolite device method will be measured. Also serum MDA and TAC will be assayed using calorimetric method. Separation of mononuclear cells by PBMC and extraction of RNA and cDNA synthesis will be done with Fermantase kits. Gene expression of PPAR-γ and adiponectin will be assayed using Real time PCR method.
Participants/Inclusion and exclusion criteria
Diabetic patients with NAFLD
Intervention groups
The use of ezetimibe and metformin in the treatment of grade 2 non- alcoholic fatty liver patients with diabetes. The intervention group receives a daily dose of 10 mg ezetimibe from Hakim pharmaceutical company and between 500-2500 mg metformin tablets from Raha pharmaceutical company and the control group will take 500-2500 mg metformin tablets daily for 6 months.
Main outcome variables
In this study , the expression of adiponectin and PPAR-γ and the level of liver enzymes, the degree of steatosis, glycemic indices and lipid profile as the primary outcomes, as well as the serum levels of TAC, MDA and interleukin 6 and anthropometric indices will be considered as secondary outcomes

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20090305001745N3
Registration date: 2023-12-03, 1402/09/12
Registration timing: prospective

Last update: 2023-12-03, 1402/09/12
Update count: 0
Registration date
2023-12-03, 1402/09/12
Registrant information
Name
Mohamad Taghi Goodarzi
Name of organization / entity
Hamadan University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 81 3838 0462
Email address
mt.goodarzi@umsha.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-12-06, 1402/09/15
Expected recruitment end date
2024-06-04, 1403/03/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Study the effect of ezetimibe along with metformin on changes in PPAR-γ and adiponectin expression, serum levels of liver enzymes, degree of hepatic steatosis, blood glycemic and lipids parameters in non-alcoholic fatty liver grade 2 patients suffering from diabetes: clinical trial
Public title
A comparative study of the use of metformin and ezetimibe compared to the use of metformin in the treatment of non-alcoholic fatty liver disease
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Type 2 diabetes is known ( under treatment) At least one year has passed since their diabetes NAFLD grade 2 or 3 has been diagnosed by ultrasound All patients should undergo non -pharmacological life style modification treatment
Exclusion criteria:
Newly diagnosed subjects Type 1 diabetes Receiving only insulin treatment Drug intolerance disorders Lack of consent to continue treatment Diagnosis of type 1 NAFLD Having a weight loss of more than 5 % Having Infectious diseases , cancer, allergy and immune - based diseases Smoking and alcohol consumption Appetite disorders such as anorexia or overeating Treatment with amphetamine, cyproheptadine, phenothiazine, appetite suppressants or appetite stimulants Chronic viral hepatitis (HBV-HCV-HDV), drug-induced liver disease , Wilson's disease , hereditary deficiency of antitrypsin 1, idiopathic hemochromatosis, history of complications from liver diseases including ascites , encephalopathy or variceal bleeding Uncontrolled cardiovascular or respiratory disease , active malignancy or active and chronic infections The use of agents such as vitamin E- omega 3 fatty acids or drugs with evidence of their effect on NAFLD (pioglitazon , GLP 1analog , dipeptidyl peptidase inhibitors IV ,ursodeoxycholic acid) Pregnancy or breastfeeding Use of corticosteroids Taking herbal medicines whose effect on fatty liver has been proven Taking any nutritional supplements in the last 3 months
Age
From 30 years old to 60 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size: 80
Randomization (investigator's opinion)
Randomized
Randomization description
Simple randomization using individual method by the Endocrinologist. The patients will be divided into groups according the number of their registration in clinic: odd numbers in control group and even numbers in intervention group.
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 Committee of Islamic Azad University of Shahrood
Street address
Daneshgah Blvd.
City
Shahrood
Province
Semnan
Postal code
3614871151
Approval date
2023-09-07, 1402/06/16
Ethics committee reference number
IR.IAU.SHAHROOD.REC.1402.043

Health conditions studied

1

Description of health condition studied
ِDiabetes
ICD-10 code
E11.6
ICD-10 code description
Type 2 diabetes mellitus with other specified complications

Primary outcomes

1

Description
Liver steatosis
Timepoint
At the beginning of intervention and 6 months after that date.
Method of measurement
Sonography

2

Description
Adiponectin gene expression
Timepoint
At the beginning of intervention and 6 months after that date
Method of measurement
Real time PCR

3

Description
PPAR- gama Gene expression
Timepoint
At the beginning of intervention and 6 months after that
Method of measurement
Real time PCR

4

Description
Activity of liver enzymes in serum
Timepoint
At the beginning of intervention and 6 months after that date
Method of measurement
Spectrophotometry

5

Description
Patients lipid profile
Timepoint
At the beginning of intervention and 6 months after that date
Method of measurement
Autoanalyzer (Spectrophotometry)

6

Description
Serum Level of IL-6
Timepoint
At the beginning of intervention and 6 months after that date
Method of measurement
Enzyme Immunoassay

7

Description
Serum Level of Malone- di-aldehyde
Timepoint
At the beginning of intervention and 6 months after that date
Method of measurement
Spectrophotometry

Secondary outcomes

1

Description
Total Antioxidant Capacity
Timepoint
At the beginning of intervention and 6 months after that date.
Method of measurement
Spectrophotometry

2

Description
Fasting blood glucose
Timepoint
At the beginning of intervention and 6 months after that date.
Method of measurement
Autoanalyzer

3

Description
2 hours post prandial glucose
Timepoint
At the beginning of intervention and 6 months after that date.
Method of measurement
Autoanalyzer

4

Description
Glycated hemoglobin (HbA1c)
Timepoint
At the beginning of intervention and 6 months after that date.
Method of measurement
Spectrophotometry

5

Description
Insulin Resistance Index ( HOMA-IR)
Timepoint
At the beginning of intervention and 6 months after that date.
Method of measurement
Calculation according to the related formula

Intervention groups

1

Description
Intervention group: grade 2 non- alcoholic fatty liver patients with diabetes receives a daily dose of 10 mg ezetimibe (Hakim pharmaceutical company )and between 500-2500 mg metformin tablets (Raha pharmaceutical company) for 6 months.
Category
Treatment - Drugs

2

Description
Control group: grade 2 non- alcoholic fatty liver patients with diabetes receives 500-2500 mg metformin tablets (Raha pharmaceutical company) for 6 months.
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Nikbakht Clinic
Full name of responsible person
Mohammad Reza Mirzaei
Street address
Nikbakht Clinic No 48, West Nikbakht St, Chaharbagh Bala St.
City
Isfahan
Province
Isfehan
Postal code
8163816651
Phone
+98 31 3132 3211
Fax
+98 31 3132 3211
Email
mohamadmirzaei@yahoo.com
Web page address
https://nikbakhtclinic.com/

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Islamic Azad University of Shahrood
Full name of responsible person
ُSahebali Manafi Dr.
Street address
Daneshgah Boulevard
City
Shahrood
Province
Semnan
Postal code
3619943189
Phone
+98 23 3239 4279
Email
info@iau-shahrood.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
No
Title of funding source
There is no financial support for this project. It will be carried out in personal expenses.
Proportion provided by this source
100
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Persons

Person responsible for general inquiries

Contact
Name of organization / entity
Islamic Azad University of Shahrood
Full name of responsible person
Mohammad Taghi Goodarzi
Position
Professor
Latest degree
Ph.D.
Other areas of specialty/work
Biochemistry
Street address
Daneshgah Boulvard
City
Shahrood
Province
Semnan
Postal code
3619943189
Phone
+98 23 3239 1890
Email
mtgoodarzi@yahoo.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Islamic Azad University of Shahrood
Full name of responsible person
Mohammad Taghi Goodarzi
Position
Professor
Latest degree
Ph.D.
Other areas of specialty/work
Biochemistry
Street address
Daneshgah Boulvard
City
Shahrood
Province
Semnan
Postal code
3619943189
Phone
+98 23 3239 1890
Email
mtgoodarzi@yahoo.com

Person responsible for updating data

Contact
Name of organization / entity
Islamic Azad University of Shahrood
Full name of responsible person
Asieh Maseli
Position
Ph.D. candidate
Latest degree
Master
Other areas of specialty/work
Biochemistry
Street address
Department of Chemistry, Faculty of Basic Sciences, Islamic Azad Universityو Daneshgah Blvd
City
Shahrood
Province
Semnan
Postal code
3619943189
Phone
+98 23 3239 4530
Email
baranm1394@gmail.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Not applicable
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