Febuxostat Versus Allopurinol on Hepatic Steatosis in MAFLD Patients

Non-Alcoholic Fatty Liver Disease Clinical Trial

Official title:

Allopurinol Versus Febuxostat: A New Approach for Management of Hepatic Steatosis in Metabolic-Associated Fatty Liver Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05474560
• Other study ID #: Febuxostat versus allopurinol
• Status: Completed
• Phase: Phase 4
• Start date: January 1, 2022
• Est. completion date: January 28, 2023

Study information

• Verified date: February 2023
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The aim of this study is to evaluate the effect of urate lowering therapy on improvement of steatosis in metabolic associated fatty liver disease (MAFLD) patients with hyperuricemia, by comparing two xanthine oxidase inhibitors allopurinol (100 mg/day), versus Febuxostat (40 mg/day), versus lifestyle intervention.

Primary Outcome: Regression of hepatic steatosis. Secondary Outcome: Improvement of Serum uric acid and incidence of hepatotoxicity.

Study design: This study is a prospective, interventional three arm study. Setting: Patients will be recruited from the National Hepatology and Tropical Medicine Research institute, Cairo, Egypt.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: January 28, 2023
• Est. primary completion date: January 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• had received systemic hormone or immunosuppressive therapy within 3 months prior to screening or expected to receive hormone or immunosuppressive therapy in the future.

• Use of other drugs affecting uric acid metabolism were adjusted within 4 weeks before screening: losartan, fenofibrate, irbesartan, thiazide diuretics, loop medullar diuretics, compound antihypertensive agents containing diuretics.

Other drugs that may affect liver fat content were taken within 4 weeks before screening.

• Women who are lactating or pregnant.

Related Conditions & MeSH terms

• Fatty Liver
• Hyperuricemia
• Liver Diseases
• Non-Alcoholic Fatty Liver Disease

Intervention

Drug:
• Allopurinol (100 mg/day) plus lifestyle intervention
participants accept allopurinol treatment (100 mg, once a day, orally). Behavioral: lifestyle intervention According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).
• Febuxostat 40 mg plus lifestyle intervention
participants accept Febuxostat treatment (100 mg, once a day, orally). Behavioral: lifestyle intervention According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).

Behavioral:
• Life style intervention
According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).

Locations

Country	Name	City	State
Egypt	National Hepatology and tropical medicine research institute	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Serum uric acid.	change in serum uric milligrams/deciliter (mg/dl) in hyperuricemia patients. Normal values are 1.5 to 6.0 (mg/dl).	three months