Comparative Study Between Febuxostat Versus Vitamin E in Non-alcoholic Steatohepatitis Patients With Hyperuricemia

NCT05574036 | Active Not Recruiting Phase 2

• 1 other identifier: 34512/2/22
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims at evaluating and comparing the protective outcomes of using Febuxostat versus Vitamin E in Hyperuricemia non-alcoholic steatohepatitis patients without cirrhosis. The intervention is 6-months duration and the study will assess the efficacy of either drug as fibrosis improvement (≥ 1 stage) with no worsening of NASH or NASH resolution with no worsening of fibrosis with the study considered successful if either 1ry end point is met. Also, assessment of biochemical markers related to steatosis, inflammation, oxidative stress, insulin resistance and liver fibrosis will be done.

Conditions

Non Alcoholic Steatohepatitis; Hyperuricemia

Keywords

Hyperuricemic NAFLD; Elevated uric acid with fatty liver

Outcome Measures

Primary Outcomes (3)

• Change in fibrosis stage; fibrosis improvement (≥ 1 stage), with no worsening of NASH, detected by fibroscan device

  Patients will undergo fibroscan testing prior to the initiation of the intervention and after 6 months of receiving the drug therapy to detect fibrosis improvement

  6 months

• Change from baseline NASH condition at 6 months; NASH resolution, with no worsening of fibrosis, with the study considered successful if either 1ry end point is met.

  Patients will undergo assessment of serum aminotransferases prior to the initiation of the intervention and after 6 months of receiving the drug therapy to detect NASH resolution

  6 months

• Change from baseline steatosis stage at 6 months detected by Fibroscan device

  Patients will undergo fibroscan testing prior to the initiation of the intervention and after 6 months of receiving the drug therapy to detect steatosis improvement

  6 months

Secondary Outcomes (9)

• Change in serum level of Nucleotide-binding and oligomerization domain (NOD-like) receptor family pyrin domain containing 3 inflammasome(NLRP3)

  6 months

• Change in serum level of Malondialdehyde (MDA)

  6 months

• Change in serum uric acid

  6 months

• Change in fasting insulin with calculation of Homeostasis Model Assessment (HOMA-IR).

  6 months

• Change in serum level of cytokeratin-18 (CK-18)

  6 months

Study Arms (2)

Group 1 Febuxostat group

ACTIVE COMPARATOR

35 non alcoholic steatohepatitis hyperuricemic patients receiving Febuxostat 80 mg once daily for 6 months duration

Drug: Febuxostat 80 MG Oral Tablet

Group 2 vitamin E group

ACTIVE COMPARATOR

35 non alcoholic steatohepatitis Hyperuricemic patients receiving vitamin E 400 mg twice daily for 6 months duration

Drug: vit E

Interventions

Febuxostat 80 MG Oral Tablet DRUG

Febuxostat used as 80 mg oral tablet once daily for 6 months

Also known as: Andouristat 80 mg, Staturic 80 mg

Group 1 Febuxostat group

vit E DRUG

Vitamin E used as 400 mg soft gelatin capsules twice daily for 6 months

Also known as: Vitamin E 400 mg

Group 2 vitamin E group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged ≥18 years.
• All patients are diagnosed to have fatty liver grading 1, 2 or 3 on abdominal ultrasound with Hepatic steatosis index \> 36 to be considered as a NAFLD patient.
• Serum uric acid level ≥ 6 mg/dl.
• Confirmed diagnosis of NASH using at least three of the following non-invasive tests:
• HAIR score
• Fibroscan detecting steatosis with F0-3 fibrosis stage
• Cytokeratin-18 \>240 U/L
• Mild to moderate elevation of serum aminotransferases (\>2 but \<5 times upper normal limit)

You may not qualify if:

• Current or history of significant alcohol consumption.
• Use of drugs historically associated with nonalcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins).
• Prior or planned bariatric surgery.
• Patients with Hemoglobin A1c 9.5% or higher.
• Evidence of other forms of chronic liver disease as Hepatitis B, Hepatitis C, Wilson's disease, Alpha-1-antitrypsin(A1AT) deficiency, Hemochromatosis, drug-induced liver disease.
• Serum creatinine of 2.0 mg/dL or greater.
• Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial and breast feeding.
• Use of other drugs known to have possible positive effects on steatosis.
• Patients on oral anticoagulants as warfarin.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine,Tanta University

Tanta, Egypt

Location

Related Publications (6)

• El Hadi H, Vettor R, Rossato M. Vitamin E as a Treatment for Nonalcoholic Fatty Liver Disease: Reality or Myth? Antioxidants (Basel). 2018 Jan 16;7(1):12. doi: 10.3390/antiox7010012.

  PMID: 29337849 BACKGROUND

• Afzali A, Weiss NS, Boyko EJ, Ioannou GN. Association between serum uric acid level and chronic liver disease in the United States. Hepatology. 2010 Aug;52(2):578-89. doi: 10.1002/hep.23717.

  PMID: 20683957 BACKGROUND

• Zhu Y, Hu Y, Huang T, Zhang Y, Li Z, Luo C, Luo Y, Yuan H, Hisatome I, Yamamoto T, Cheng J. High uric acid directly inhibits insulin signalling and induces insulin resistance. Biochem Biophys Res Commun. 2014 May 16;447(4):707-14. doi: 10.1016/j.bbrc.2014.04.080. Epub 2014 Apr 21.

  PMID: 24769205 BACKGROUND

• Tang W, Mu J, Chen QI, Li X, Liu H. The involvement and mechanism of febuxostat in non-alcoholic fatty liver disease cells. J Biol Regul Homeost Agents. 2018 May-Jun;32(3):545-551.

  PMID: 29921379 BACKGROUND

• Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Jan;67(1):328-357. doi: 10.1002/hep.29367. Epub 2017 Sep 29. No abstract available.

  PMID: 28714183 BACKGROUND

• El-Sheikh H, El-Haggar S, Badawi R, Habba E. Comparative efficacy of febuxostat and vitamin E in the management of MASLD: Insights from a randomized parallel clinical study. Eur J Pharmacol. 2025 Aug 5;1000:177735. doi: 10.1016/j.ejphar.2025.177735. Epub 2025 May 16.

  PMID: 40383220 DERIVED

Related Links

• Effects of Febuxostat for Lowering Uric Acid in NAFLD Patients With Gout
• Vitamin E and NAFLD

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Hyperuricemia

Interventions

Febuxostat; Tablets; Vitamin E

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Hadier m. El-sheikh

  Department of Clinical pharmacy, Faculty of Pharmacy, Tanta university

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecturer of clinical pharmacy- Clinical pharmacy department- Faculty of pharmacy

Model Details: This study is randomized controlled, parallel and prospective 6-months duration study. Accepted patients will be randomized into 2 groups as the following: * Group 1 (Febuxostat group): 35 patients will receive 80 mg/day febuxostat for 6 months. * Group 2 (Control group): 35 patients will receive Vitamin E 400 mg twice daily for 6 months.

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 10, 2022
• Study Start: August 25, 2022
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): December 25, 2026
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)