Follow-up of NAFLD Patients With MRI-PDFF

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

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.

Study Overview

• Status: Completed
• Conditions: NAFLD; Diabetes Type 2
• Intervention / Treatment: Drug: Empagliflozin 25 MG; Drug: Pentoxifylline 400 MG; Drug: Ursodeoxycholic acid; Other: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Minya, Egypt, 61118
    • Minya university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

    1. History of recurrent attacks of UTI or Genital infection in females
    2. History of recurrent foot injuries or infections
    3. Type 2 diabetic patient with CV disease especially NYHA classes III/ IV
    4. Immunocompromised patients or with a history of inflammatory, immunological, or malignant diseases.

  • Any contraindication for PTX including:

    1. Hypersensitivity to PTX
    2. Patients with peptic ulcer disease or tendency for bleeding

  • Any contraindication for UDCA including:

    1. Hypersensitivity to UDCA
    2. Patients with biliary disease or hepatobiliary disease (ascites, jaundice)
    3. Patients with hepatic encephalopathy or gallstone pancreatitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Asmaa Abdelfattah Elsayed
• Investigators: Principal Investigator: Asmaa A Elsayed, PhD, BUC

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 28, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Estimate): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 17, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Gastrointestinal Agents; Protective Agents; Sodium-Glucose Transporter 2 Inhibitors; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Cholagogues and Choleretics; Empagliflozin; Ursodeoxycholic Acid; Pentoxifylline
• Other Study ID Numbers: BeniSuef

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes