Follow-up of NAFLD Patients With MRI-PDFF

Study Overview
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Brief Summary
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The liver is a key organ in metabolism and contributes to T2DM development and insulin resistance via unclear mechanisms that may involve liver fat accumulation, inflammatory signals, and immune cells are proposed to play an important role in the pathogenesis of both NAFLD and T2DM.

Detailed Description
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This study aims to define The effects of PTX, Empagliflozin as an example of SGLT-2 inhibitors and UDCA on liver biomarkers and liver steatosis in type 2 diabetic patients. Studying PTX, Empagliflozin as an example of SGLT-2 inhibitors and UDCA efficacy and safety as add-on therapy in type 2 diabetic patients.

Official Title
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Evaluating the Effect of Pentoxifylline, Ursodiol, and Empagliflozin on Fatty Liver of Patients With Type-2 Diabetes

Conditions
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Diabetes Type 2, NAFLD

Intervention / Treatment
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* Drug: Empagliflozin 25 MG
* Drug: Ursodeoxycholic acid
* Drug: Pentoxifylline 400 MG
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are willing to participate in this study Adults aged ≥ 18 years old presented at the clinic with a confirmed diagnosis of T2DM who are on sulfonylurea for the last 6 months at least and diagnosed with NAFLD. Exclusion Criteria: • Patients who refused to participate in this trial Patients diagnosed with Type 1 diabetes Previous history of alcohol intake history of recurrent attacks of ketoacidosis in a diabetic patient Type 2 diabetic patient with kidney dysfunction (estimated eGFR below 60ml/min/1.73m2 or CrCl below 60ml/min) or on dialysis Previous history of taking medication that may alter either drug efficacy (eg, corticosteroids, oral contraceptives, and thiazide diuretics) Evidence of another liver disease (viral hepatitis, drug-induced liver disease, autoimmune hepatitis) Lactating/pregnant female or children ≤ 18 Any contraindication for Empagliflozin including: History of recurrent attacks of UTI or Genital infection in females History of recurrent foot injuries or infections Type 2 diabetic patient with CV disease especially NYHA classes III/ IV Immunocompromised patients or with a history of inflammatory, immunological, or malignant diseases. Any contraindication for PTX including: Hypersensitivity to PTX Patients with peptic ulcer disease or tendency for bleeding Any contraindication for UDCA including: Hypersensitivity to UDCA Patients with biliary disease or hepatobiliary disease (ascites, jaundice) Patients with hepatic encephalopathy or gallstone pancreatitis

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Empa group<br>patients will be given Empagliflozin 25 mg once daily | Drug: Empagliflozin 25 MG<br>* tablets to be taken orally once a day<br>* Other names: Jardiance 25mg tablets;|
| Experimental: PTX group<br>patients will be given PTX 400 mg twice daily or 3 times daily | Drug: Pentoxifylline 400 MG<br>* tablets to be taken orally twice a day<br>* Other names: Trental tablets;|
| Experimental: UDCA group<br>patients will be given UDCA 500 mg twice daily | Drug: Ursodeoxycholic acid<br>* tablets to be taken orally twice a day<br>* Other names: Ursofalk tablets;|
| Placebo Comparator: Placebo<br>patients will be given a placebo | Other: placebo<br>* just starch tablets without any active agents<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| liver fat content (percent) | measured by MRI-PDFF | 6-months | 
| fatty liver staging (0, I, II, and III) | using ultrasound | 6-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Serum Gamma glutamyl transferase (γ-GT) | IU/l | 6-months | 
| HbA1c (%) |  | 6-months | 
| Fasting and 2-hr post-prandial serum glucose (mg/dl) |  | 6-months | 
| Lipid profile | (serum triglycerides, total cholesterol, LDL, HDL) (mg/dl) | 6-months | 
| Changes in liver enzymes | AST (IU/l) and ALT (IU/l) | 6-months | 
| Changes in direct and total bilirubin | (mg/dl) | 6-months | 
| Changes in total protein and albumin | (g/l) | 6-months |