Uric Acid and the Endothelium is CKD

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by University of Colorado, Denver
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01228903
First received: October 25, 2010
Last updated: September 25, 2012
Last verified: September 2012
  Purpose

This study will test the hypothesis that uric acid impairs the function of vessels in patients with kidney disease


Condition Intervention
Kidney Disease
Drug: Allopurinol
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Is Uric Acid a Mediator of Endothelial Dysfunction in Patients With Chronic Kidney Disease?

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Endothelial Dependent Dilation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Endothelial Dependent Dilation measured by Flow Mediated Dilation


Secondary Outcome Measures:
  • Systemic inflammation and oxidative stress [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Inflammation will be measured by plasma levels of the following: hs- CRP, interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1). Oxidized low density lipoprotein cholesterol (oxLDL), asymmetric dimethylarginine (ADMA), and 8-isoprostanes, as markers of oxidative stress.

  • Inflammation and oxidative stress in the endothelial cells [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Actual measurements: intercellular adhesion molecule (ICAM-1) and nuclear factor kappa-B (NFkappa-B p65), nitrotyrosine, Nox4-containing NAD(P)H oxidase complexes, and endothelial nitric oxide synthase (eNOS).


Estimated Enrollment: 80
Study Start Date: October 2010
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Control
Patients who are randomized to this group will received placebo tablets. Placebo tables do not contain an active ingredient. This group will be used as a baseline group to compare the effects of lowering uric acid on vascular function.
Other: Placebo
Placebo tablets with no active ingredient
Active Comparator: Allopurinol
Patients who are randomized to this group will receive allopurinol tablets. Allopurinol is a medicine that lowers uric acid levels. The effects of lowering uric acid on vascular function outcomes will be assessed and compared to the control group.
Drug: Allopurinol
Xanthine oxidase inhibitor- effective at lowering uric acid levels.
Other Name: Zyloprim, Allohexal, Allosig, Milurit, Alloril, Progout, Zyloric.

Detailed Description:

The purpose of the study is to understand the effect of lowering serum uric acid levels on vascular function in individuals with chronic kidney disease by comparing the effects of:

1) Allopurinol therapy and 2) Placebo.

Patients will receive: 3 month study drug (either allopurinol or placebo), with assessment of serum uric acid levels and vascular function.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Individuals with moderate chronic kidney disease (CKD stage III) with estimated glomerular filtration rates between 30-60 mL/min/ 1.73m2
  • Elevated uric acid levels
  • Age range: more than 18 years old
  • Ability to give informed consent
  • Albumin > 3.0 g/dL
  • BMI < 40 kg/m2

Exclusion Criteria:

  • Life expectancy < 1.0 years
  • Expected to undergo living related kidney transplant in 6 months
  • Pregnant, breast feeding, or unwilling to use adequate birth control
  • History of severe liver disease
  • History of severe congestive heart failure
  • History of hospitalizations within 3 months
  • Active infection, on antibiotics
  • History of Warfarin Use or other medications that are contraindicated with allopurinol
  • Uncontrolled hypertension
  • History of acute gout on Allopurinol
  • History of adverse reaction to Allopurinol
  • Immunosuppressive therapy within the last 1 yr
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01228903

Contacts
Contact: Diana I Jalal, MD 3037244867 diana.jalal@ucdenver.edu
Contact: Michel Chonchol, MD 3033996997 michel.chonchol@ucdenver.edu

Locations
United States, Colorado
University of Colorado at Denver Recruiting
Aurora, Colorado, United States, 80045
Contact: Diana I Jalal, MD    303-724-4867    diana.jalal@ucdenver.edu   
Contact: Michel Chonchol, MD    3033996997    michel.chonchol@ucdenver.edu   
Principal Investigator: Diana I Jalal, MD         
Sub-Investigator: Michel Chonchol, MD         
Sub-Investigator: Richard J Johnson, MD         
Sub-Investigator: Tomas Berl, MD         
Sub-Investigator: Kim McFann, PhD         
Sponsors and Collaborators
University of Colorado, Denver
  More Information

Additional Information:
No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01228903     History of Changes
Other Study ID Numbers: 10-0625, K23DK088833
Study First Received: October 25, 2010
Last Updated: September 25, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
uric acid kidney disease endothelial dysfunction

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Allopurinol
Uric Acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Antimetabolites
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014