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Urate Lowering Therapies and Left Ventricular Diastolic Dysfunction

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ClinicalTrials.gov Identifier: NCT03534037
Recruitment Status : Active, not recruiting
First Posted : May 23, 2018
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
Cheng-Wei Liu, National Defense Medical Center, Taiwan

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

Condition or disease Intervention/treatment Phase
Hyperuricemia Metabolic Syndrome Left Ventricular Diastolic Dysfunction Drug: Febuxostat 40 mg Drug: Benzbromarone 50mg Other: Control Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Cardiovascular Effects of Febuxostat and Benzbromarone on Left Ventricle Diastolic Dysfunction in Individuals With Metabolic Syndrome and Hyperuricemia - an Open-label Non-blinded Randomized-controlled Clinical Trial
Actual Study Start Date : December 3, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Febuxostat

Arm Intervention/treatment
Experimental: Febuxostat 40mg
Febuxostat 40mg orally per day
Drug: Febuxostat 40 mg
Febuxostat 40 mg orally per day plus dietary control only
Other Name: Feburic

Active Comparator: Benzbromarone 50mg
Benzbromarone 50mg orally per day
Drug: Benzbromarone 50mg
Benzbromarone 50mg orally per day plus dietary control only
Other Name: Nogout

Control
Dietary control only
Other: Control
Dietary control only




Primary Outcome Measures :
  1. Change of average E/e' [ Time Frame: At day1 and at week 12 ]
    the mean change of average E/e' in each group

  2. Difference of average E/e' [ Time Frame: At day1 and at week 12 ]
    the mean difference of average E/e' between among three groups


Secondary Outcome Measures :
  1. Change of xanthine oxidase activity [ Time Frame: At day1 and at week 12 ]
    the mean change of xanthine oxidase activity in each group

  2. Difference of xanthine oxidase activity [ Time Frame: At day1 and at week 12 ]
    the mean difference of xanthine oxidase activity among three groups

  3. Change of left ventricular mass index [ Time Frame: At day1 and at week 12 ]
    the mean change of left ventricular mass index in each group

  4. Difference of left ventricular mass index [ Time Frame: At day1 and at week 12 ]
    the mean difference of left ventricular mass index among three groups

  5. Change of tumor necrosis factor alpha [ Time Frame: At day1 and at week 12 ]
    the mean change of tumor necrosis factor alpha in each group

  6. Difference of tumor necrosis factor alpha [ Time Frame: At day1 and at week 12 ]
    the mean difference of tumor necrosis factor alpha among three groups

  7. Change of high-sensitivity interleukin-6 [ Time Frame: At day1 and at week 12 ]
    the mean change of high-sensitivity interleukin-6 in each group

  8. Difference of high-sensitivity interleukin-6 [ Time Frame: At day1 and at week 12 ]
    the mean difference of high-sensitivity interleukin-6 among three groups

  9. Change of thioredoxin [ Time Frame: At day1 and at week 12 ]
    the mean change of Thioredoxin in each group

  10. Difference of Thioredoxin [ Time Frame: At day1 and at week 12 ]
    the mean difference of Thioredoxin among three group

  11. Change of fibroblast growth factor 23 [ Time Frame: At day1 and at week 12 ]
    the mean Change of fibroblast growth factor 23 in each group

  12. Difference of fibroblast growth factor 23 [ Time Frame: At day1 and at week 12 ]
    the mean difference of fibroblast growth factor 23 among three groups

  13. Change of Dickkopf-related protein 3 [ Time Frame: At day1 and at week 12 ]
    the mean change of Dickkopf-related protein 3 in each group

  14. Difference of Dickkopf-related protein 3 [ Time Frame: At day1 and at week 12 ]
    the mean difference of Dickkopf-related protein 3 among three groups

  15. Change of galectin-3 [ Time Frame: At day1 and at week 12 ]
    the mean change of galectin-3 in each group

  16. Difference of galectin-3 [ Time Frame: At day1 and at week 12 ]
    the mean difference of galectin-3 among three groups

  17. Change of ST2 [ Time Frame: At day1 and at week 12 ]
    the mean change of ST2 in each group

  18. Difference of ST2 [ Time Frame: At day1 and at week 12 ]
    the mean difference of ST2 among three groups



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03534037


Locations
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Taiwan
Tri-service General Hospital, songshan branch
Taipei, Songshan Dist., Taiwan, 105
Sponsors and Collaborators
National Defense Medical Center, Taiwan
Investigators
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Principal Investigator: Cheng-Wei Liu, M.D. 1.Tri-service General hospital, Songshan branch, Taipei, Taiwan

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Responsible Party: Cheng-Wei Liu, Principal investigator, National Defense Medical Center, Taiwan
ClinicalTrials.gov Identifier: NCT03534037     History of Changes
Other Study ID Numbers: 1-107-05-112
First Posted: May 23, 2018    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Cheng-Wei Liu, National Defense Medical Center, Taiwan:
Serum uric acid
Metabolic syndrome
Left ventricular diastolic dysfunction
Febuxostat
Benzbromarone

Additional relevant MeSH terms:
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Febuxostat
Syndrome
Metabolic Syndrome
Hyperuricemia
Ventricular Dysfunction, Left
Disease
Pathologic Processes
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Ventricular Dysfunction
Heart Diseases
Cardiovascular Diseases
Benzbromarone
Gout Suppressants
Antirheumatic Agents
Uricosuric Agents
Renal Agents