Non-Alcoholic Fatty Liver DiseasePhase 4NCT05474560
Febuxostat Versus Allopurinol on Hepatic Steatosis in MAFLD Patients
A Phase 4 study testing Allopurinol (100 mg/day) plus lifestyle intervention, Febuxostat 40 mg plus lifestyle intervention and Life style intervention in people with Non-Alcoholic Fatty Liver Disease and Hyperuricemia, run by Ain Shams University at 1 site in Egypt.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Hyperuricemia
- What is being tested?
- Allopurinol (100 mg/day) plus lifestyle intervention, Febuxostat 40 mg plus lifestyle intervention and Life style intervention
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jan 2022to 28 Jan 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Allopurinol Versus Febuxostat: A New Approach for Management of Hepatic Steatosis in Metabolic-Associated Fatty Liver Disease
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.
Read the 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.
- Conditions
- Non-Alcoholic Fatty Liver Disease, Hyperuricemia
- Being tested
- Allopurinol (100 mg/day) plus lifestyle intervention, Febuxostat 40 mg plus lifestyle intervention, Life style intervention
- Keywords
- Fatty liver disease, Hyperuricemia, Allopurinol, Febuxostat
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Hyperuricemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allopurinol (100 mg/day) plus lifestyle interventionDrug
Also called Allopurinol group
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 interventionDrug
Also called Febuxostat group
participants accept Febuxostat treatment (100 mg, once a day, orally). Behavioral: lifestyle intervention According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).
Life style interventionBehavioural
According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise).
| Study group | Role | What they receive |
|---|---|---|
| Allopurinol group | Experimental | Allopurinol (100 mg/day) plus lifestyle intervention Receives: Drug: Allopurinol (100 mg/day) plus lifestyle intervention |
| Febuxostat group | Experimental | Febuxostat (40 mg/day) plus lifestyle intervention Receives: Drug: Febuxostat 40 mg plus lifestyle intervention |
| lifestyle intervention | Active comparator | diet and exercise Receives: Behavioral: Life style intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Secondary outcomes (1)
Serum uric acid.
change in serum uric milligrams/deciliter (mg/dl) in hyperuricemia patients. Normal values are 1.5 to 6.0 (mg/dl).
Measured: three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2022
- Study start1 Jan 2022
- Primary completion28 Jan 2023
- Study completion28 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sarah Ma Zaki, Ass.Prof., Study director, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05474560
- Sponsor's protocol ID
- Febuxostat versus allopurinol
- Status last verified
- Feb 2023
- First submitted
- 13 Jul 2022
- Last updated
- 1 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26395162Younossi 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.
PubMed 28930295Darmawan 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.
PubMed 28790228Allen 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.
PubMed 28941364Turnheim 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.
PubMed 10583019Lee 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.
PubMed 30442825Moy 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.
PubMed 21054885Kuo 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.
PubMed 20560813Hallsworth 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.
PubMed 32039399Harrison 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.
PubMed 17911352
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allopurinol Versus Febuxostat: A New Approach for Management of Hepatic Steatosis in Metabolic-Associated Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT05474560
- Acronym / sponsor ID
- Febuxostat versus allopurinol
- Conditions
- Non-Alcoholic Fatty Liver Disease, Hyperuricemia
- Keywords
- Fatty liver disease, Hyperuricemia, Allopurinol, Febuxostat
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 28 Jan 2023 (actual)
- Study completion
- 28 Jan 2023 (actual)
- First posted
- 26 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Allopurinol group | Experimental | Drug: Allopurinol (100 mg/day) plus lifestyle interventionAllopurinol (100 mg/day) plus lifestyle intervention |
| Febuxostat group | Experimental | Drug: Febuxostat 40 mg plus lifestyle interventionFebuxostat (40 mg/day) plus lifestyle intervention |
| lifestyle intervention | Active comparator | Behavioral: Life style interventiondiet and exercise |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- Serum uric acid levels of > 420μmol/L (>7 mg/dL) in men and >360 μmol/L (>6 mg/dL) women.
Key exclusion criteria (19 listed)
- Renal insufficiency defined by serum creatinine > 2.0 mg/dl.
- Other drugs that may affect liver fat content were taken within 4 weeks before screening.
- Women who are lactating or pregnant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allopurinol (100 mg/day) plus lifestyle interventionAlso: Allopurinol groupparticipants accept allopurinol treatment (100 mg, once a day, orally). Behavioral: lifestyle intervention According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise). | Drug | Allopurinol group |
| Febuxostat 40 mg plus lifestyle interventionAlso: Febuxostat groupparticipants accept Febuxostat treatment (100 mg, once a day, orally). Behavioral: lifestyle intervention According to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise). | Drug | Febuxostat group |
| Life style interventionAccording to NAFLD guidelines, participants receive lifestyle intervention (diet and exercise). | Behavioural | lifestyle intervention |
Primary outcome
Change in hepatic steatosis .
Time frame: 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.
1 secondary outcome
Serum uric acid.
Time frame: three months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
- Background: PubMed 26395162Liu 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.
- Background: PubMed 28930295Younossi 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.
- Background: PubMed 28790228Darmawan 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.
- Background: PubMed 28941364Allen 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.
- Background: PubMed 10583019Turnheim 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.
- Background: PubMed 30442825Lee 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.
- Background: PubMed 21054885Moy 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.
- Background: PubMed 20560813Kuo 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.
- Background: PubMed 32039399Hallsworth 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.
- Background: PubMed 17911352Harrison 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sarah Ma Zaki, Ass.Prof. study director
Ain Shams University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Allopurinol (100 mg/day) plus lifestyle intervention, Febuxostat 40 mg plus lifestyle intervention and Life style intervention in people with Non-Alcoholic Fatty Liver Disease and Hyperuricemia, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in hepatic steatosis . (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05474560, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2023.