Effects of Febuxostat on Adipokines and Kidney Disease in Diabetic Chronic Kidney Disease

NCT01350388 | Completed Results DMC

• 1 other identifier: IRB_00044016
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Hyperuricemia is emerging as a risk factor for development of diabetes and metabolic syndrome. Recently, it was shown in in-vitro cell culture experiments that hyperuricemia induces redox-dependent signaling and oxidative stress in adipocytes. By targeting levels of uric acid with febuxostat it is hypothesized that the levels of oxidative stress in adipose tissue (obtained by fat biopsy) will decrease. Primary aims of the study are to determine whether febuxostat therapy in overweight or obese, diabetic patients with stage 3 Chronic Kidney Disease (CKD) and high serum uric acid levels

1. 1.will affect adipose tissue concentrations of thiobarbituric acid reactive substance (TBARS), a marker of oxidative stress
2. 2.will affect adipose tissue expression and concentrations of adiponectin; and
3. 3.will affect urinary concentrations of transforming growth factor (TGF)- B1.

Conditions

Chronic Kidney Disease; Diabetes

Keywords

Chronic Kidney Disease; Diabetes; Febuxostat; Inflammation; Hyperuricemia

Outcome Measures

Primary Outcomes (3)

• Change in Thiobarbituric Acid Reactive Substance (TBARS) Concentration in Adipose Tissue From Baseline to 24 Weeks

  The percent difference in thiobarbituric acid reactive substance (TBARS) concentration geometric mean values from baseline to 24 weeks was calculated for each arm

  Baseline and 24 weeks

• Change in Adiponectin Concentration in Adipose Tissue From Baseline to 24 Weeks

  The percent difference in adiponectin concentration geometric mean values from baseline to 24 weeks was calculated for each arm

  Baseline and 24 weeks

• Change in Urinary Concentrations of Transforming Growth Factor-beta1 (TGF-beta1) From Baseline to 24 Weeks

  The percent difference in TGF-beta1 concentration geometric mean values from baseline to 24 weeks was calculated for each arm

  Baseline and 24 weeks

Secondary Outcomes (3)

• Change in Tumor Necrosis Factor-α (TNF-α) Concentration in Plasma From Baseline to 24 Weeks

  Baseline and 24 weeks

• Change in Interleukin-6 (IL-6) Concentration in Plasma From Baseline to 24 Weeks

  Baseline and 24 weeks

• Change in High Sensitivity C-Reactive Protein (hsCRP) Concentration in Plasma From Baseline to 24 Weeks

  Baseline and 24 weeks

Study Arms (2)

Febuxostat

ACTIVE COMPARATOR

80 mg/day of febuxostat for 24 weeks

Drug: Febuxostat

Placebo

PLACEBO COMPARATOR

1 placebo tablet per day for 24 weeks

Drug: Placebo

Interventions

Febuxostat DRUG

80 mg/day of febuxostat for 24 weeks

Also known as: Uloric

Febuxostat

Placebo DRUG

1 placebo tablet per day for 24 weeks

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• BMI \> 25 kg/m2
• type 2 diabetes
• serum uric acid ≥ 5.5 mg/dl in men and ≥ 4.6 mg/dl in women
• eGFR 30-60 mL/min/1.73m2

You may not qualify if:

• History of gout
• concurrent use of azathioprine, mercaptopurine, theophylline, allopurinol, thiazolidinediones or warfarin
• concurrent use of metformin
• current antibiotic therapy
• pregnant women
• prisoners

Sponsors & Collaborators

• University of Utah: lead
• Takeda: collaborator

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Beddhu S, Filipowicz R, Wang B, Wei G, Chen X, Roy AC, DuVall SL, Farrukh H, Habib AN, Bjordahl T, Simmons DL, Munger M, Stoddard G, Kohan DE, Greene T, Huang Y. A Randomized Controlled Trial of the Effects of Febuxostat Therapy on Adipokines and Markers of Kidney Fibrosis in Asymptomatic Hyperuricemic Patients With Diabetic Nephropathy. Can J Kidney Health Dis. 2016 Dec 5;3:2054358116675343. doi: 10.1177/2054358116675343. eCollection 2016.

  PMID: 28270924 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Diabetes Mellitus; Inflammation; Hyperuricemia

Interventions

Febuxostat

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Srinivasan Beddhu, M.D.
• Organization: University of Utah

srinivansan.beddhu@hsc.utah.edu

801-585-3810

Study Officials

• Srinivasan Beddhu, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Srinivasan Beddhu, MD Associate Professor of Medicine

Study Record Dates

• First Submitted: April 20, 2011
• First Posted: May 9, 2011
• Study Start: May 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: December 1, 2013
• Last Updated: October 3, 2016
• Results First Posted: October 3, 2016

Record last verified: 2016-08

Locations

US (1)