Healthy VolunteersPhase 1NCT01323335
The Relationship Between Uric Acid and Inflammatory Markers
A Phase 1 study testing IV Uric Acid and IV Rasburicase in people with Healthy Volunteers, run by National Institute on Aging (NIA) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- IV Uric Acid and IV Rasburicase
- Type of treatment
- Injection or infusion
- How many people
- 97 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Mar 2009to 31 Jan 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 29Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Aging, Clinical Research Unit
Baltimore, Maryland, 21224
About this study
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.
Read more
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.
Read the detailed description
Uric acid (UA) is a terminal product of purine metabolism with strong antioxidant properties. UA has sizeable concentrations in biologic fluids only in humans and primates because they have a non-functional mutation of the enzyme uricase that, in other animals, transforms UA to allantoin. It has been hypothesized that this mutation has emerged evolutionarily because through this mechanism, humans can counteract the excessive oxidative stress that occurs in many critical pathologic conditions. Partially in contrast with this theory, high levels of UA have been associated with a number of negative health outcomes, including cardiovascular as well as all-cause mortality. Although it is possible that the UA elevation is merely a marker of critical health because it is an inducible antioxidant, researchers have questioned whether UA has beneficial or detrimental effect on health status. For example, we recently demonstrated that higher UA levels are cross-sectionally associated with higher levels of pro-inflammatory markers, and predict the increase in inflammatory markers over a 3-year follow-up. Understanding whether UA exerts a protective or detrimental effect on health is important in deciding whether mild hyperuricemia should or should not be aggressively treated.
Unfortunately, observational studies cannot fully address this question. In fact, we cannot exclude that the cross-sectional and longitudinal association between UA, inflammatory markers and negative health outcomes, may simply reflect the fact that UA is an inducible antioxidant that is produced in response to increasing oxidative stress. To verify the hypothesis that UA activates inflammation, we plan to conduct two complementary randomized controlled trials, each one including 10 treated and 10 control subjects. In the first trials, subjects with low UA will be administered 500 mg of UA intravenously. In the second trials, subjects with moderately elevated UA will be administered a single acute dose of Rasburicase. Then inflammatory markers will be measured at multiple points in time, for a total of 32 hours. We hypothesize that an acute increase in the circulating levels of UA will be followed by increasing levels of inflammatory markers. At the same time, an acute reduction of UA levels will be followed by a progressive reduction of inflammatory markers. This study should provide information that will help clinicians to decide whether to or not to treat mild hyperuricemia.
- Conditions
- Healthy Volunteers
- Being tested
- IV Uric Acid, IV Rasburicase
- Keywords
- Uric Acid, Rasburicase, Inflammatory Markers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV Uric AcidDrug
IV RasburicaseDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of uric acid on inflammatory markers
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2011 (estimated)
- Study start31 Mar 2009
- Primary completion31 Jan 2014
- Study completion31 Jan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Aging (NIA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Luigi Ferrucci, M.D., Principal investigator, National Institute on Aging (NIA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01323335
- Sponsor's protocol ID
- 999909322
- Other IDs
- 09-AG-N322
- Status last verified
- 31 Jan 2014
- First submitted
- 24 Mar 2011
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
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.
PubMed 12908717Carnethon 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.
PubMed 14630601Kahn 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.
PubMed 5075070Tanaka 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.
PubMed 28786993
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relationship Between Uric Acid and Inflammatory Markers
- ClinicalTrials.gov ID
- NCT01323335
- Acronym / sponsor ID
- 999909322
- Conditions
- Healthy Volunteers
- Keywords
- Uric Acid, Rasburicase, Inflammatory Markers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- 31 Mar 2009
- Primary completion
- 31 Jan 2014 (actual)
- Study completion
- 31 Jan 2014 (actual)
- First posted
- 25 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Uric acid (UA) is a terminal product of purine metabolism with strong antioxidant properties. UA has sizeable concentrations in biologic fluids only in humans and primates because they have a non-functional mutation of the enzyme uricase that, in other animals, transforms UA to allantoin. It has been hypothesized that this mutation has emerged evolutionarily because through this mechanism, humans can counteract the excessive oxidative stress that occurs in many critical pathologic conditions. Partially in contrast with this theory, high levels of UA have been associated with a number of negative health outcomes, including cardiovascular as well as all-cause mortality. Although it is possible that the UA elevation is merely a marker of critical health because it is an inducible antioxidant, researchers have questioned whether UA has beneficial or detrimental effect on health status. For example, we recently demonstrated that higher UA levels are cross-sectionally associated with higher levels of pro-inflammatory markers, and predict the increase in inflammatory markers over a 3-year follow-up. Understanding whether UA exerts a protective or detrimental effect on health is important in deciding whether mild hyperuricemia should or should not be aggressively treated.
Unfortunately, observational studies cannot fully address this question. In fact, we cannot exclude that the cross-sectional and longitudinal association between UA, inflammatory markers and negative health outcomes, may simply reflect the fact that UA is an inducible antioxidant that is produced in response to increasing oxidative stress. To verify the hypothesis that UA activates inflammation, we plan to conduct two complementary randomized controlled trials, each one including 10 treated and 10 control subjects. In the first trials, subjects with low UA will be administered 500 mg of UA intravenously. In the second trials, subjects with moderately elevated UA will be administered a single acute dose of Rasburicase. Then inflammatory markers will be measured at multiple points in time, for a total of 32 hours. We hypothesize that an acute increase in the circulating levels of UA will be followed by increasing levels of inflammatory markers. At the same time, an acute reduction of UA levels will be followed by a progressive reduction of inflammatory markers. This study should provide information that will help clinicians to decide whether to or not to treat mild hyperuricemia.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IV Uric Acid | Drug | – |
| IV Rasburicase | Drug | – |
Primary outcome
Effects of uric acid on inflammatory markers
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 12908717Nakanishi 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.
- Background: PubMed 14630601Carnethon 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.
- Background: PubMed 5075070Kahn 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.
- Derived from this study: PubMed 28786993Tanaka 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luigi Ferrucci, M.D. principal investigator
National Institute on Aging (NIA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IV Uric Acid and IV Rasburicase in people with Healthy Volunteers, run by National Institute on Aging (NIA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effects of uric acid on inflammatory markers. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01323335, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2018.