Hyperuricemia, Metabolic Syndrome, Left Ventricular Diastolic Dysfunction
Conditions
Keywords
Serum uric acid, Metabolic syndrome, Left ventricular diastolic dysfunction, Febuxostat, Benzbromarone
Brief summary
Hyperuricemia is an additional risk factor for cardiovascular disease, associating with left ventricular diastolic dysfunction in individuals with metabolic syndrome. The effect of urate-lowering therapies on left ventricular diastolic dysfunction remains unclear. The study is conducted to investigate whether febuxostat or benzbromarone might improve left ventricular diastolic dysfunction in individuals with metabolic syndrome and hyperuricemia
Detailed description
Between 1, July 2018 and 31, Dec 2018, consecutive individuals with metabolic syndrome hyperuricemia are candidates of the present study. After the eligible candidates sign the informed consent, they will receive blood tests with a fasting time of 8 hours at least. The investigators will randomize the study participants by pre-specified random codes with a 1:1:1 ratio to the three groups. The study medication, febuxostat or benzbromarone, will be administered orally on the next day after transthoracic echocardiography is performed. The control group will only receive dietary control. All participant will receive transthoracic echocardiography and blood tests at baseline and at 3 months. The visit will be scheduled at baseline and at the 3rd month. The blood tests include high-sensitivity C-reactive protein, high-sensitivity interleukin-1 beta, high-sensitivity interleukin-6, tumor necrosis factor alpha, Dickkopf-related protein 3, galectin-3, ST2, fibroblast growth factor 23, xanthine oxidase activity, and thioredoxin.
Interventions
DRUGFebuxostat 40 mg
Febuxostat 40 mg orally per day plus dietary control only
DRUGBenzbromarone 50mg
Benzbromarone 50mg orally per day plus dietary control only
OTHERControl
Dietary control only
Sponsors
National Defense Medical Center, Taiwan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
(all of the four criteria) 1. Aged between 40-75 years 2. Metabolic syndrome 3. Hyperuricemia, defined as a serum uric acid level of 7 mg/dl or more in men or 6 mg/dl or more in females, with a history of hyperuricemia within a year; or a serum uric acid level of 8 mg/dl or more in men or 7 mg/dl or more in females and it is hardly expected to be modified by dietary control; or persistent hyperuricemia after dietary control for 3 months 4. Not take any of urate-lowering therapies (benzbromarone, allopurinol, or febuxostat)
Exclusion criteria
1. pregnancy 2. hypersensitivity to febuxostat or benzbromarone 3. acute gout 4. a history of urinary tract stone 5. chronic kidney disease stage IV or V 6. valvular heart disease with moderate or severe regurgitation 7. left ventricular ejection fraction of 40% or less 8. hypertrophic cardiomyopathy or dilated cardiomyopathy or infiltrative cardiomyopathy or constrictive cardiomyopathy 9. a history of congenital heart disease 10. a history of pulmonary hypertension 11. chronic atrial fibrillation or significant arrhythmia 12. a history of intracardiac device implantation 13. uncontrolled hypertension (systolic blood pressure \> 160mm Hg or diastolic blood pressure \> 100 mm Hg) 14. alanine Aminotransferase \> 3 times upper limit) 15. acute infection 16. suspected or diagnosed with malignancy 17. a history of autoimmune disease 18. limited to or dependent on daily activities 19. life expectancy less than a year 20. Acute coronary syndrome or received a percutaneous coronary intervention or received a coronary artery graft bypass surgery or stroke within 3 months 21. Diabetes with insulin treatment or glucagon-like peptide 1 receptor agonist treatment 22. Anemia (hemoglobin \< 11 mg/dl in mem or \<10mg/dl in women)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of average E/e' | At day1 and at week 12 | the mean change of average E/e' in each group |
| Difference of average E/e' | At day1 and at week 12 | the mean difference of average E/e' between among three groups |
| Automate office blood pressure (AOBP) | At day1 and at week 12 | the mean difference of AOBP among three groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference of left ventricular mass index | At day1 and at week 12 | the mean difference of left ventricular mass index among three groups |
| Change of tumor necrosis factor alpha | At day1 and at week 12 | the mean change of tumor necrosis factor alpha in each group |
| Difference of tumor necrosis factor alpha | At day1 and at week 12 | the mean difference of tumor necrosis factor alpha among three groups |
| Change of high-sensitivity interleukin-6 | At day1 and at week 12 | the mean change of high-sensitivity interleukin-6 in each group |
| Difference of high-sensitivity interleukin-6 | At day1 and at week 12 | the mean difference of high-sensitivity interleukin-6 among three groups |
| Change of thioredoxin | At day1 and at week 12 | the mean change of Thioredoxin in each group |
| Difference of Thioredoxin | At day1 and at week 12 | the mean difference of Thioredoxin among three group |
| Change of xanthine oxidase activity | At day1 and at week 12 | the mean change of xanthine oxidase activity in each group |
| Difference of fibroblast growth factor 23 | At day1 and at week 12 | the mean difference of fibroblast growth factor 23 among three groups |
| Change of Dickkopf-related protein 3 | At day1 and at week 12 | the mean change of Dickkopf-related protein 3 in each group |
| Difference of Dickkopf-related protein 3 | At day1 and at week 12 | the mean difference of Dickkopf-related protein 3 among three groups |
| Change of galectin-3 | At day1 and at week 12 | the mean change of galectin-3 in each group |
| Difference of galectin-3 | At day1 and at week 12 | the mean difference of galectin-3 among three groups |
| Change of ST2 | At day1 and at week 12 | the mean change of ST2 in each group |
| Difference of ST2 | At day1 and at week 12 | the mean difference of ST2 among three groups |
| Change of fibroblast growth factor 23 | At day1 and at week 12 | the mean Change of fibroblast growth factor 23 in each group |
| Difference of xanthine oxidase activity | At day1 and at week 12 | the mean difference of xanthine oxidase activity among three groups |
| Change of left ventricular mass index | At day1 and at week 12 | the mean change of left ventricular mass index in each group |
Countries
Taiwan
Contacts
Primary ContactCheng-Wei Liu, M.D.
Outcome results
None listed