Febuxostat Versus Allopurinol on Hepatic Steatosis in MAFLD Patients

Sponsor

Ain Shams University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05474560

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Fatty Liver Disease Hyperuricemia	Drug: Allopurinol (100 mg/day) plus lifestyle intervention Drug: Febuxostat 40 mg plus lifestyle intervention Behavioral: Life style intervention	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Febuxostat Versus Allopurinol on Hepatic Steatosis in Metabolic Associated Fatty Liver Disease

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Allopurinol group Allopurinol (100 mg/day) plus lifestyle 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).
Experimental: Febuxostat group Febuxostat (40 mg/day) plus lifestyle intervention	Drug: 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).
Active Comparator: lifestyle intervention diet and exercise	Behavioral: Life style intervention According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).

Arm

Intervention/Treatment

Experimental: Allopurinol group

Allopurinol (100 mg/day) plus lifestyle 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).

Experimental: Febuxostat group

Febuxostat (40 mg/day) plus lifestyle intervention

Drug: 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).

Active Comparator: lifestyle intervention

diet and exercise

Behavioral: Life style intervention

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

Outcome Measures

Primary Outcome Measures

Change in hepatic steatosis . [3 months]
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.

Secondary Outcome Measures

Serum uric acid. [three months]
change in serum uric milligrams/deciliter (mg/dl) in hyperuricemia patients. Normal values are 1.5 to 6.0 (mg/dl).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.