The Relationship Between Uric Acid and Inflammatory Markers

• Status: Completed
• Trial end date: 2014-01-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute on Aging (NIA)
• Treatments: Rasburicase; Uric Acid

Criteria

• INCLUSION CRITERIA:

• 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

EXCLUSION CRITERIA:

• 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

• Hb <11.5 g/dL in women or < 12.5 g/dL in men

• Acute infection/inflammation (CRP>5 mcg/mL) for Trial A: UA versus Placebo, CRP >10mcg/L for Trial B: -Rasburicase versus Placebo, or any clinical overt chronic infections including periodontal disease.

• Active liver disease or liver function tests greater than 2 times upper normal limit

• Self reported inflammatory joints or autoimmune diseases

• Treatment over the last 3 months with Allopurinol, Rasburicase

• Treatment over the last 3 months with Warfarin, Dicumarol, Theophylline, Statins

• Necessity of daily treatment with NSAID

• Current hormone replacement

• Ongoing glucocorticoids, corticosteroids, including prednisone and/or cortisone injections or inhalations. (topical steroid cream use and occasional corticosteroid administration over the last 3 months is acceptable)

• Current daily antioxidants or/and multivitamin supplementation or over the last month

• Life-threatening diseases including malignancies

• Recent Blood Donation (last 56 days)

• Any other reason that based on the PI's judgment requires exclusion from this study

• Inability to obtain venous access.