NCT01323335

Brief Summary

Background: \- Uric acid is a substance found in the blood that may contribute to certain chronic medical conditions and disorders, such as diabetes, insulin resistance, and high blood pressure. High uric acid concentrations have been associated with stroke and heart disease, as well as chronic heart failure. In particular, researchers are interested in determining the relationship between uric acid and inflammatory markers, or chemicals in the blood that can indicate inflammation and other problems with the body. Objectives:

  • To study the specific effects of changes in uric acid in the body.
  • To determine whether uric acid contributes to inflammation in the body. Eligibility: \- Healthy individuals between 50 and 75 years of age. Design:
  • This study will involve four visits: a screening visit, two study visits, and a followup visit.
  • At the screening visit, participants will have a physical examination, blood and urine tests, and an electrocardiogram. Participants will be divided into two groups based on the existing amount of uric acid in their blood.
  • Within 7 days of the screening visit, participants will have a full-day study visit with a magnetic resonance imaging scan, followed by a high-fat meal and further blood samples collected over the following 8 hours.
  • At least 2 days after the first study visit, participants will have the second study visit, which will require a 2-night stay at the National Institutes of Health. Participants will have a metabolism test, and will receive the following infusions based on the groups they were assigned to at the screening visit.
  • Group A (low uric acid) will receive either uric acid or a placebo.
  • Group B (moderate to high uric acid) will receive either Rasburicase (a drug that reduces the amount of uric acid in the blood) or a placebo.
  • After the infusions and related blood tests, participants will have a high-fat meal with further blood and urine samples.
  • Approximately 2 weeks after the second study visit, participants will have a final followup visit with additional blood and urine tests to determine whether the levels of uric acid in the blood have returned to normal.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
97

participants targeted

Target at P75+ for phase_1 healthy-volunteers

Timeline
Completed

Started Mar 2009

Longer than P75 for phase_1 healthy-volunteers

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 31, 2009

Completed
2 years until next milestone

First Submitted

Initial submission to the registry

March 24, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 25, 2011

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2014

Completed
Last Updated

July 5, 2018

Status Verified

January 31, 2014

Enrollment Period

4.8 years

First QC Date

March 24, 2011

Last Update Submit

July 3, 2018

Conditions

Healthy Volunteers

Keywords

Uric AcidRasburicaseInflammatory Markers

Outcome Measures

Primary Outcomes (1)

  • Effects of uric acid on inflammatory markers

Interventions

IV Uric AcidDRUG
IV RasburicaseDRUG

Eligibility Criteria

Age50 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 50-75 years
  • BMI 23-30 kg/m(2)
  • Estimated GFR \>60 mL/min
  • Blessed mental score equal to or less than 3
  • Ability to fully participate in an informed consent process
  • For Trial A (UA versus Placebo): all participants should have UA\<6 mg/dL
  • For Trial B (Rasburicase versus Placebo): all participants should have UA 6.0-10 mg/dL

You may not qualify if:

  • History of hypersensibility or intolerance to Rasburicase and/or to Lithium
  • Chronic Kidney Disease.
  • History of kidney stones.
  • History of asthma, atopic allergies, hemolytic or methemoglobinemia reactions
  • History of unstable angina, cardiac arrhythmia, stroke or myocardial infarction within 3 months, open-heart surgery within 6 months of the study enrollment
  • History of drug or alcohol dependence, or positive urine toxicology
  • Past or present positive test for HBV, HCV or HIV (base on blood test).
  • Glucose-6-Phosphate Dehydrogenase deficiency (G6PD-deficiency)
  • History of gout
  • Last menstruation occurred less than 1 year ago
  • Unintentional or intentional weight loss of 5 kg in the previous 6 months
  • Alcohol daily intake \>30 grams (more than 2 beers daily, more than 2 glass of wine or cocktail daily)
  • Current smokers or former smokers (stopped smoking less than 1 year before)
  • Blood pressure \> 150/90 mmHg
  • Diabetes mellitus on dietary or pharmacological treatment
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institute of Aging, Clinical Research Unit

Baltimore, Maryland, 21224, United States

Location

Related Publications (4)

  • Nakanishi N, Okamoto M, Yoshida H, Matsuo Y, Suzuki K, Tatara K. Serum uric acid and risk for development of hypertension and impaired fasting glucose or Type II diabetes in Japanese male office workers. Eur J Epidemiol. 2003;18(6):523-30. doi: 10.1023/a:1024600905574.

    PMID: 12908717BACKGROUND

  • Carnethon MR, Fortmann SP, Palaniappan L, Duncan BB, Schmidt MI, Chambless LE. Risk factors for progression to incident hyperinsulinemia: the Atherosclerosis Risk in Communities Study, 1987-1998. Am J Epidemiol. 2003 Dec 1;158(11):1058-67. doi: 10.1093/aje/kwg260.

    PMID: 14630601BACKGROUND

  • Kahn HA, Medalie JH, Neufeld HN, Riss E, Goldbourt U. The incidence of hypertension and associated factors: the Israel ischemic heart disease study. Am Heart J. 1972 Aug;84(2):171-82. doi: 10.1016/0002-8703(72)90331-6. No abstract available.

    PMID: 5075070BACKGROUND

  • Tanaka T, Milaneschi Y, Zhang Y, Becker KG, Zukley L, Ferrucci L. A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study. PLoS One. 2017 Aug 7;12(8):e0181100. doi: 10.1371/journal.pone.0181100. eCollection 2017.

    PMID: 28786993DERIVED

MeSH Terms

Interventions

Uric Acidrasburicase

Intervention Hierarchy (Ancestors)

XanthinesAlkaloidsHeterocyclic CompoundsPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Luigi Ferrucci, M.D.

    National Institute on Aging (NIA)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
CROSSOVER
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 24, 2011

First Posted

March 25, 2011

Study Start

March 31, 2009

Primary Completion

January 31, 2014

Study Completion

January 31, 2014

Last Updated

July 5, 2018

Record last verified: 2014-01-31

Locations

US(1)