Dapagliflozin in Type 2 Diabetes Mellitus Patients (T2DM) With Nonalcoholic Fatty Liver Disease (NAFLD)

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effect of dapagliflozin on liver function of patient with NAFLD and T2DM.

Detailed Description
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Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University. Ethical committee approval will be obtained from Ethics committee of General Organization for Teaching Hospitals and Institutes. About 50 patients who are candidate to detect the hepato-protective effect of Dapagliflozin on non- alcoholic fatty disease, will be recruited from Alexandria Teaching Hospital (EL-Mery), General Organization for Teaching Hospitals and Institutes. All participants should agree to take part in this clinical study and will provide informed consent. Demographic data; age (year), sex (female/male), weight (kg), height (cm), BMI (kg/m2) will be collected. Venous blood samples (5 ml will be collected by a sterile syringe then placed in a suitable sterile tube to be centrifuged, the serum will be reserved and stored at -80°C until the analysis) before, and after receiving medication (Dapagliflozin). Measuring outcome: The biochemical tests will be done on the patients are alanine aminotransferase (ALT), aspartate aminotransferase (AST), homeostasis model assessment of insulin resistance (HOMA-IR), Hemoglobin A1C (HbA1C), Low-density lipoproteins (LDL), High-density lipoproteins (HDL), Triglycerides (TG), liver fibrosis score, and complete blood count (CBC). The molecular tests will be done on the patient are soluble vascular cell adhesion molecule-1 (Svcam-1), adipocytes (e.g. adiponectin, leptin). The ultrasound screening will be done at first examination. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results. Results, conclusion, discussion and recommendations will be given.

Official Title
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The Hepato-protective Effect of Dapagliflozin in Type 2 Diabetes Mellitus Patients (T2DM) With Nonalcoholic Fatty Liver Disease (NAFLD)

Conditions
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Type 2 Diabetes, Nonalcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: Dapagliflozin 10mg Tab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus patients. HbA1C < 8.5. Patients were They were having fatty liver changes on abdominal ultrasound and mild to moderate elevation of serum liver enzymes. BMI more than 30 Exclusion Criteria: Patients with a history of alcohol, smoking, uncontrolled diabetes. (HbA1c > 9.0). Pregnancy. Lactation. Hemochromatosis. Thyroid disorders. Renal dysfunction. Cardiac problem. Chronic liver and decompensated liver disease in the form of hepatitis B and C.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective, randomized (1:1), double-blind clinical trial, will be carried out on 50 patients who are candidate to detect the hepato-protective effect of Dapagliflozin on diabetic type 2 patients with non- alcoholic fatty disease (dapagliflozin 10 mg once daily for 24 - 48 weeks -Patients will be randomly allocated into two equal groups (25 patients each); group (A) for controlled (placebo), and the other group (D) for Dapagliflozin.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: group (A) for controlled (placebo).<br>25 patients will recieve placebo for 6 months. | Other: Placebo<br>* Placebo<br>|
| Active Comparator: group (D) for Dapagliflozin.<br>25 patients will recieve 10 mg Dapagliflozin daily for 6 months. | Drug: Dapagliflozin 10mg Tab<br>* Dapagliflozin 10 mg once daily for 24 weeks.<br>* Other names: Dapagliflozin 10 mg.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| leptin (ng/ml) | leptin by enzyme-linked immunosorbent assay (ELISA). | 6 months | 
| adiponectin (pg/ml) | adiponectin by enzyme-linked immunosorbent assay (ELISA). | 6 months | 
| VCAM-1 (ng/ml) | VCAM-1 was analyzed in serum using the human VCAM-1 ELISA kits. | 6 months |