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Febuxostat, Blood Pressure and the Intrarenal Renin-Angiotensin System (RAS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Paul N. Hopkins, University of Utah
ClinicalTrials.gov Identifier:
NCT01328769
First received: March 29, 2011
Last updated: May 13, 2013
Last verified: May 2013
History of Changes
  Purpose

In this study the investigators will recruit hypertensive subjects with higher than average uric acid levels to test the effect of lowering uric acid with febuxostat on several measures as listed below. This will be a randomized, double-blind, placebo-controlled, parallel group study.

Primary Aim

1. To examine the effects of febuxostat on the activity of the intrarenal renin-angiotensin system as measured indirectly by renal plasma flow response to infused Ang II.

Secondary Aims

  1. To examine the effects of febuxostat on proximal and distal tubular sodium excretion as estimated by uric acid clearance and sodium clearance.
  2. To determine effects of febuxostat on endothelial function in hypertensive subjects with higher than average uric acid.
  3. To determine effect of febuxostat on blood pressure (by 24-hour ambulatory monitoring).

3. To examine the correlation between change in uric acid and changes in inflammatory markers including hsCRP and (optionally) other markers of endothelial activation including soluble ICAM-1, VCAM-1, and MCP-1.


Condition Intervention Phase
Hypertension
 Drug: Febuxostat
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Febuxostat, Blood Pressure and the Intrarenal Renin-Angiotensin System (RAS)

Resource links provided by NLM:

Drug Information available for: Febuxostat
U.S. FDA Resources

Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Change in renal plasma flow in response to infused angiotensin II [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in endothelial function [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: March 2011
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Febuxostat Drug: Febuxostat
This will be a randomized, double-blind, placebo-controlled, parallel group trial. Baseline measurements will be performed initially off all antihypertensive medication and without study medication. Subjects will then be randomized to febuxostat or placebo, treated for 6 weeks, and baseline measurements will then be repeated to assess change from baseline.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Mild to moderate hypertension. For purposes of this study, the investigators define mild to moderate hypertension as being on no more than 1-2 antihypertensive medications and blood pressure <140 mm Hg systolic and <90 mm Hg diastolic based on mean seated blood pressure at the screening visit in our clinic. For these visits, the investigators measure blood pressure using a Dinamap automatic oscillometric cuff while subjects are seated quietly. The subjects are left in a quiet room without speaking for 5 minutes initially. The Dinamap is started and the technician leaves the room and 3 blood pressures are obtained at intervals of 2 minutes. The investigators use the mean of last 2 blood pressures for classification purposes. This is the approach the investigators have used in several multicenter studies including HyperGEN and the NHLBI Family Heart Study.
  • Age 18 to 60.
  • Uric acid =5.8 mg/dl. This was the mean uric acid among hypertensives in our prior study.11 As renal plasma flow response to Ang II infusion decreased linearly with higher uric acid, the investigators felt that using higher than average uric acid will provide greater power.

Exclusion Criteria:

  • Severe or poorly controlled hypertension (treated blood pressure >160 mm Hg systolic or >100 mm Hg diastolic).
  • Diabetes (type 1 or type 2).
  • Estimated GFR <60 ml/min.
  • Persons unable stop all medications (including antihypertensives) other than stable doses of thyroxine or estrogen for at least 2 weeks.
  • Secondary hypertension.
  • Prior history of clinically diagnosed coronary artery disease or congestive heart failure.
  • Taking uric acid lowering medication within 1 month of screening visit.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01328769

Locations
United States, Utah
Cardiovascular Genetics, University of Utah
Salt Lake City, Utah, United States, 84108
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Paul N Hopkins Cardiovascular Genetics
  More Information

No publications provided

Responsible Party: Paul N. Hopkins, Professor of Internal Medicine, University of Utah
ClinicalTrials.gov Identifier: NCT01328769     History of Changes
Other Study ID Numbers: 42916
Study First Received: March 29, 2011
Last Updated: May 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
uric acid
febuxostat
hypertension
 intra-renal renin-angiotensin system
renal plasma flow
angiotensin II

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Febuxostat
 Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013