Effects of Febuxostat for Lowering Uric Acid in NAFLD Patients With Gout

Effects of Febuxostat for Interventions of Lowering Uric Acid in Patients With Gout With Nonalcoholic Fatty Liver Disease: a Multicenter, Open-label, Randomized, Controlled Study

Nonalcoholic fatty liver disease (NAFLD) is the most common and harmful chronic liver disease. NAFLD accounts for 49.3% of the total number of chronic liver disease patients in China. It is important to effectively prevent and control NAFLD and its related diseases.

Previous studies show the level of serum uric acid is significantly elevated in patients with NAFLD. Xanthine oxidase is a key enzyme in uric acid metabolism. It is a new therapeutic target for NAFLD.

This study is aimed to further confirm that hyperuricemia is a new risk factor for NAFLD through a large sample prospective study. Furthermore, this study explore whether Xanthine oxidase (XO), a key enzyme in uric acid metabolism, plays an important role in regulating NAFLD.

Study Overview

• Status: Not yet recruiting
• Conditions: Nonalcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: febuxostat treatment; Behavioral: lifestyle intervention

Detailed Description

Nonalcoholic fatty liver disease (NAFLD) is the most common and harmful chronic liver disease. NAFLD accounts for 49.3% of the total number of chronic liver disease patients in China. It is important to effectively prevent and control NAFLD and its related diseases.

Previous studies show the level of serum uric acid is significantly elevated in patients with NAFLD. In a large cross-sectional study, the researcher were the first to confirm that serum uric acid level was significantly increased in patients with NAFLD. The results were published in J Hepatol. Xanthine oxidase is a key enzyme in uric acid metabolism. It is a new therapeutic target for NAFLD.

This study is aimed to further confirm that hyperuricemia is a new risk factor for NAFLD through a large sample prospective study. Furthermore, this study explore whether Xanthine oxidase (XO), a key enzyme in uric acid metabolism, plays an important role in regulating NAFLD.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Ningbo, Zhejiang, China, 315000
      • Ningbo First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• with informed consent;
• Ages 18-65;
• Overweight/obesity: BMI ≥24kg/m2;
• A history of gout with serum uric acid levels of > 420μmol/L in men and postmenopausal women, and >360 μmol/L in premenopausal women;
• Moderate or above fatty liver was found in the initial screening by ultrasound, and the liver fat content was more than 15% as determined by MRI-PDFF.

Exclusion Criteria:

• with 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);
• Patients with obvious abnormal liver function: serum transaminase (ALT, AST, GGT one of them) or serum bilirubin (direct bilirubin, indirect bilirubin one of them) exceed 2 times the upper limit of normal reference value; Serum albumin <35g/L;
• Have a history of viral hepatitis, or serological examination suggests hepatitis virus infection, or have a history of other liver diseases;
• Complicated with renal insufficiency (SCr >133μmol/L) or urinary protein +;
• Complicated coronary heart disease;
• Cardiac dysfunction (cardiac function grade 2 or above);
• Complementation with diabetes, or fasting blood glucose >7.8mmol/L, or HbA1c >7.5%;
• Severe hypertension, blood pressure ≥ 160/100 mmHg;
• Patients with asthma and other respiratory diseases;
• Intestinal diseases such as inflammatory bowel disease;
• Any history of systemic malignancy in the past 5 years;
• 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 uric-lowering drugs in the 4 weeks before screening: febuxostat, benzobromarone, allopurinol;
• Use of other drugs affecting uric acid metabolism were adjusted within 4 weeks before screening: losartan, fenofibrate, irbesartan, thiazide diuretics, loop medullaral diuretics, compound antihypertensive agents containing diuretics;
• Other drugs that may affect liver fat content were taken within 4 weeks before screening;
• Weight change ≥5% within 3 months before screening;
• Women who are lactating or pregnant or who plan to become pregnant within one year;
• were enrolled in other studies within 6 months before screening;
• unsuitable for participants to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group: Lifestyle intervention + febuxostat (40mg, once a day, orally); participants accept febuxostat treatment in addition to lifestyle intervention for 0-48 week.	Drug: febuxostat treatment; According to NAFLD guidelines, participants accept febuxostat treatment (40mg, once a day, orally); Behavioral: lifestyle intervention; According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).
Active Comparator: Control group: Lifestyle intervention; participants receive lifestyle intervention for 0-24 week. If the results of the 0-24 week study showed that the liver fat content of subjects in the experimental group was significantly lower than that in the control group, control group will accept febuxostat treatment in addition to lifestyle intervention in the next 25-48 week.	Behavioral: lifestyle intervention; According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver fat content of subjects in different groups	Liver fat was assessed based on Magnetic Resonance Imaging (MRI).	at the first week.
Liver fat content of subjects in different groups	Liver fat was assessed based on Magnetic Resonance Imaging (MRI).	at the 24th week .
Liver fat content of subjects in different groups	Liver fat was assessed based on Magnetic Resonance Imaging (MRI).	at the 48th week.
Serum uric acid levels of subjects in different groups	blood samples was assessed after 12 hours overnight fasting for the determination of hematological and biochemical variables, which were measured using an automated hematology analyzer by standard methods.	at the first week
Serum uric acid levels of subjects in different groups	blood samples was assessed after 12 hours overnight fasting for the determination of hematological and biochemical variables, which were measured using an automated hematology analyzer by standard methods.	at the forth week.
Serum uric acid levels of subjects in different groups	blood samples was assessed after 12 hours overnight fasting for the determination of hematological and biochemical variables, which were measured using an automated hematology analyzer by standard methods.	at the twelfth week.
Serum uric acid levels of subjects in different groups	blood samples was assessed after 12 hours overnight fasting for the determination of hematological and biochemical variables, which were measured using an automated hematology analyzer by standard methods.	at the 24th week.
Serum uric acid levels of subjects in different groups	blood samples was assessed after 12 hours overnight fasting for the determination of hematological and biochemical variables, which were measured using an automated hematology analyzer by standard methods.	at the 36th week.
Serum uric acid levels of subjects in different groups	blood samples was assessed after 12 hours overnight fasting for the determination of hematological and biochemical variables, which were measured using an automated hematology analyzer by standard methods.	at the 48th week.

Collaborators and Investigators

• Sponsor: Ningbo No. 1 Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2021
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: February 24, 2021
• First Posted (Actual): February 26, 2021

Study Record Updates

• Last Update Posted (Actual): February 26, 2021
• Last Update Submitted That Met QC Criteria: February 24, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Antirheumatic Agents; Gout Suppressants; Febuxostat
• Other Study ID Numbers: SUANAFLD V1.0

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: No
• Studies a U.S. FDA-regulated device product: No