Febuxostat Versus Allopurinol on Hepatic Steatosis in MAFLD Patients

NCT05474560 | Completed Phase 4 DMC

• 1 other identifier: Febuxostat versus allopurinol
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic associated fatty liver disease (MAFLD) is the most common and harmful chronic liver disease, and it is increasingly diagnosed in many developed and developing countries. Previous studies suggested a significant association between hyperuricemia and MAFLD and that hyperuricemia plays a causal role in the development of MAFLD. Xanthine oxidase is a key enzyme in uric acid metabolism, and It thus can be considered as is a therapeutic target for MAFLD, so long-term urate-lowering therapy may play a role in amelioration of MAFLD by controlling uric acid levels. So, this study is conducted to assess the effect of controlling hyperuricemia using different xanthine oxidase inhibitors on amelioration of MAFLD.

Conditions

Non-Alcoholic Fatty Liver Disease; Hyperuricemia

Keywords

Fatty liver disease; Hyperuricemia; Allopurinol; Febuxostat

Outcome Measures

Primary Outcomes (1)

• Change in hepatic steatosis .

  FibroScan instrument measures fibrosis (scarring) and steatosis (fatty changes) in your liver. Fatty changes are when fat builds up in your liver cells. FibroScan steatosis result (CAP score): decibels per meter(dB/M). it ranges from 100 to 400 dB/m. The fibrosis result is measured in kilopascals (kpa). It is normaly between 2 and 6 kpa.

  3 months

Secondary Outcomes (1)

• Serum uric acid.

  three months

Study Arms (3)

Allopurinol group

EXPERIMENTAL

Allopurinol (100 mg/day) plus lifestyle intervention

Drug: Allopurinol (100 mg/day) plus lifestyle intervention

Febuxostat group

EXPERIMENTAL

Febuxostat (40 mg/day) plus lifestyle intervention

Drug: Febuxostat 40 mg plus lifestyle intervention

lifestyle intervention

ACTIVE COMPARATOR

diet and exercise

Behavioral: Life style intervention

Interventions

Allopurinol (100 mg/day) plus lifestyle intervention DRUG

participants accept allopurinol treatment (100 mg, once a day, orally). Behavioral: lifestyle intervention According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).

Also known as: Allopurinol group

Allopurinol group

Febuxostat 40 mg plus lifestyle intervention DRUG

participants accept Febuxostat treatment (100 mg, once a day, orally). Behavioral: lifestyle intervention According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).

Also known as: Febuxostat group

Febuxostat group

Life style intervention BEHAVIORAL

According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).

lifestyle intervention

Eligibility Criteria

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

You may qualify if:

• Ages 18-65.
• Males and Females
• Metabolic syndrome according to the NCEP ATP III definition \[13\]: present of three or more of the following five criteria are met:
• Waist circumference over 40 inches (men) or 35 inches (women), Central obesity - defined as waist circumference ≥ 102 cm for Men and ≥ 88 cm for women
• Blood pressure over 130/85 mmHg,
• Basting triglyceride (TG) level over 150 mg/dl,
• Fasting high-density lipoprotein (HDL) cholesterol level less than 40 mg/dl (men) or 50 mg/dl (women),
• Fasting blood sugar over 100 mg/dl.
• Serum uric acid levels of \> 420μmol/L (\>7 mg/dL) in men and \>360 μmol/L (\>6 mg/dL) women.

You may not qualify if:

• Renal insufficiency defined by serum creatinine \> 2.0 mg/dl.
• Patients with obvious abnormal liver function: serum transaminase (ALT, AST, one of them) exceed 2 times the upper limit of normal reference value.
• Have a history of viral hepatitis, or serological examination suggests hepatitis virus infection, or have a history of other liver diseases.
• Complementation with diabetes, or fasting blood glucose \>7.8mmol/L, or HbA1c \>7.5%.
• Severe hypertension, blood pressure ≥ 160/100 mmHg.
• A history of allergy to febuxostat and allopurinol; in the acute active phase of gout.
• Drinking equivalent to alcohol intake ≥30g/d(male), ≥20g/d(female).
• Complicated coronary heart disease.
• Cardiac dysfunction (cardiac function grade 2 or above).
• Patients with asthma and other respiratory diseases.
• Intestinal diseases such as inflammatory bowel disease.
• Any history of systemic malignancy in the past 5 years.
• Use of uric-lowering drugs in the 4 weeks before screening: febuxostat, allopurinol, benzbromarone.
• Morbid obesity (BMI\>37.5kg/m2).
• Triglyceride ≥5.0 mmol/L was found to be significantly abnormal in baseline examination.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

National Hepatology and tropical medicine research institute

Cairo, Egypt

Location

Related Publications (10)

• Liu Z, Que S, Zhou L, Zheng S. Dose-response Relationship of Serum Uric Acid with Metabolic Syndrome and Non-alcoholic Fatty Liver Disease Incidence: A Meta-analysis of Prospective Studies. Sci Rep. 2015 Sep 23;5:14325. doi: 10.1038/srep14325.

  PMID: 26395162 BACKGROUND

• Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J, Bugianesi E. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018 Jan;15(1):11-20. doi: 10.1038/nrgastro.2017.109. Epub 2017 Sep 20.

  PMID: 28930295 BACKGROUND

• Darmawan G, Hamijoyo L, Hasan I. Association between Serum Uric Acid and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis. Acta Med Indones. 2017 Apr;49(2):136-147.

  PMID: 28790228 BACKGROUND

• Allen AM, Therneau TM, Larson JJ, Coward A, Somers VK, Kamath PS. Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year-community study. Hepatology. 2018 May;67(5):1726-1736. doi: 10.1002/hep.29546. Epub 2018 Mar 23.

  PMID: 28941364 BACKGROUND

• Turnheim K, Krivanek P, Oberbauer R. Pharmacokinetics and pharmacodynamics of allopurinol in elderly and young subjects. Br J Clin Pharmacol. 1999 Oct;48(4):501-9. doi: 10.1046/j.1365-2125.1999.00041.x.

  PMID: 10583019 BACKGROUND

• Lee JS, Won J, Kwon OC, Lee SS, Oh JS, Kim YG, Lee CK, Yoo B, Hong S. Hepatic Safety of Febuxostat Compared with Allopurinol in Gout Patients with Fatty Liver Disease. J Rheumatol. 2019 May;46(5):527-531. doi: 10.3899/jrheum.180761. Epub 2018 Nov 15.

  PMID: 30442825 BACKGROUND

• Moy FM, Bulgiba A. The modified NCEP ATP III criteria maybe better than the IDF criteria in diagnosing Metabolic Syndrome among Malays in Kuala Lumpur. BMC Public Health. 2010 Nov 6;10:678. doi: 10.1186/1471-2458-10-678.

  PMID: 21054885 BACKGROUND

• Kuo CF, Yu KH, Luo SF, Chiu CT, Ko YS, Hwang JS, Tseng WY, Chang HC, Chen HW, See LC. Gout and risk of non-alcoholic fatty liver disease. Scand J Rheumatol. 2010 Nov;39(6):466-71. doi: 10.3109/03009741003742797. Epub 2010 Jun 21.

  PMID: 20560813 BACKGROUND

• Hallsworth K, Adams LA. Lifestyle modification in NAFLD/NASH: Facts and figures. JHEP Rep. 2019 Nov 5;1(6):468-479. doi: 10.1016/j.jhepr.2019.10.008. eCollection 2019 Dec.

  PMID: 32039399 BACKGROUND

• Harrison SA, Day CP. Benefits of lifestyle modification in NAFLD. Gut. 2007 Dec;56(12):1760-9. doi: 10.1136/gut.2006.112094. Epub 2007 Oct 2. No abstract available.

  PMID: 17911352 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Hyperuricemia

Interventions

Allopurinol; Febuxostat

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Sarah Ma Zaki, Ass.Prof.

  Ain Shams University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A total of 90 subjects are enrolled in this study. After the initial screening, the subjects were randomly divided into the control group and the drug treatment group. The control group was given lifestyle intervention for 24 weeks, and the experimental group was given febuxostat oral therapy or allopurinol oral therapy on the basis of lifestyle intervention.

Study Record Dates

• First Submitted: July 13, 2022
• First Posted: July 26, 2022
• Study Start: January 1, 2022
• Primary Completion: January 28, 2023
• Study Completion: January 28, 2023
• Last Updated: August 1, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)