Chronic Kidney DiseaseNCT01350388
Effects of Febuxostat on Adipokines and Kidney Disease in Diabetic Chronic Kidney Disease
A study testing Febuxostat in people with Chronic Kidney Disease and Diabetes, run by University of Utah at 1 site in United States.
Trial summary
Hyperuricemia is emerging as a risk factor for development of diabetes and metabolic syndrome. Recently, it was shown in in-vitro cell culture experiments that hyperuricemia induces redox-dependent signaling and oxidative stress in adipocytes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Disease, Diabetes
- What is being tested?
- Febuxostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- May 2011to Dec 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years
- BMI > 25 kg/m2
- type 2 diabetes
- serum uric acid ≥ 5.5 mg/dl in men and ≥ 4.6 mg/dl in women
- eGFR 30-60 mL/min/1.73m2
Who cannot join
- History of gout
- concurrent use of azathioprine, mercaptopurine, theophylline, allopurinol, thiazolidinediones or warfarin
- concurrent use of metformin
- current antibiotic therapy
- pregnant women
- prisoners
Trial locations and contacts
1 site in 1 country.
About this study
Hyperuricemia is emerging as a risk factor for development of diabetes and metabolic syndrome. Recently, it was shown in in-vitro cell culture experiments that hyperuricemia induces redox-dependent signaling and oxidative stress in adipocytes. By targeting levels of uric acid with febuxostat it is hypothesized that the levels of oxidative stress in adipose tissue (obtained by fat biopsy) will decrease.
Primary aims of the study are to determine whether febuxostat therapy in overweight or obese, diabetic patients with stage 3 Chronic Kidney Disease (CKD) and high serum uric acid levels
- will affect adipose tissue concentrations of thiobarbituric acid reactive substance (TBARS), a marker of oxidative stress
- will affect adipose tissue expression and concentrations of adiponectin; and
- will affect urinary concentrations of transforming growth factor (TGF)- B1.
Read the detailed description
Hyperuricemia is highly prevalent in the US population and commonly clusters with obesity and metabolic syndrome. It remains controversial whether this reflects an epiphenomenon or connotes a causal role of hyperuricemia in metabolic syndrome. If indeed hyperuricemia plays a causal role in metabolic syndrome, it would be expected that hyperuricemia will impact on the molecular signals that mediate the effects of adiposity on inflammation and insulin resistance.
Adipokines, the protein hormones produced by the adipocytes, serve as the signals for the effects of adipocytes on insulin resistance, dyslipidemia, hypertension, inflammation and atherosclerosis. Adipokines include tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), plasminogen activator inhibitor (PAI-1), leptin, angiotensinogen and adiponectin. In obesity, the production of TNF-α, IL-6, PAI-1, leptin and angiotensinogen increases whereas the production of adiponectin decreases. Increased expression of pro-inflammatory TNF-α and IL-6 and decreased expression of anti-inflammatory adiponectin by adipocytes results in insulin resistance and inflammation.
As oxidative stress in adipose tissue is considered to play a critical role in dysregulation of adipokines production in obesity and that hyperuricemia induces oxidative stress in adipocytes, it is hypothesized that hyperuricemia alters adipose tissue production of adipokines; therefore, febuxostat therapy will decrease hyperuricemia and thereby, have beneficial effects on adipokine production by adipose tissue; the favorable effects on adipokine production by febuxostat therapy will result in decrease in plasma levels of markers of inflammation; and as a result of the above, urinary markers of kidney disease will improve.
Chronic Kidney Disease (CKD) patients with type 2 diabetes will be studies because this population has a high prevalence of hyperuricemia and likely represents a target population which might benefit from reduction of uric acid levels.
This is a placebo-controlled, double-blinded, randomized controlled trial to examine the effects of uric acid lowering with oral febuxostat on adipokines and markers of inflammation.
- Conditions
- Chronic Kidney Disease, Diabetes
- Being tested
- Febuxostat, Placebo
- Keywords
- Chronic Kidney Disease, Diabetes, Febuxostat, Inflammation, Hyperuricemia
- Medical subject headings
- Renal Insufficiency, Chronic, Diabetes Mellitus, Inflammation, Hyperuricemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FebuxostatDrug
Also called Uloric
80 mg/day of febuxostat for 24 weeks
PlaceboDrug
1 placebo tablet per day for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Febuxostat | Active comparator | 80 mg/day of febuxostat for 24 weeks Receives: Drug: Febuxostat |
| Placebo | Placebo comparator | 1 placebo tablet per day for 24 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Thiobarbituric Acid Reactive Substance (TBARS) Concentration in Adipose Tissue From Baseline to 24 Weeks
The percent difference in thiobarbituric acid reactive substance (TBARS) concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Measured: Baseline and 24 weeks
Change in Adiponectin Concentration in Adipose Tissue From Baseline to 24 Weeks
The percent difference in adiponectin concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Measured: Baseline and 24 weeks
Change in Urinary Concentrations of Transforming Growth Factor-beta1 (TGF-beta1) From Baseline to 24 Weeks
The percent difference in TGF-beta1 concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Measured: Baseline and 24 weeks
Secondary outcomes (3)
Change in Tumor Necrosis Factor-α (TNF-α) Concentration in Plasma From Baseline to 24 Weeks
The percent difference in plasma TNF-α concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Measured: Baseline and 24 weeks
Change in Interleukin-6 (IL-6) Concentration in Plasma From Baseline to 24 Weeks
The percent difference in plasma IL-6 concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Measured: Baseline and 24 weeks
Change in High Sensitivity C-Reactive Protein (hsCRP) Concentration in Plasma From Baseline to 24 Weeks
The percent difference in plasma hsCRP concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Measured: Baseline and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2011 (estimated)
- Study startMay 2011
- Primary completionOct 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Responsible party
- Principal investigator, Srinvasan Beddhu, University of Utah
- Investigators
- Srinivasan Beddhu, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01350388
- Sponsor's protocol ID
- IRB_00044016
- Status last verified
- Aug 2016
- First submitted
- 20 Apr 2011
- Last updated
- 3 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Beddhu S, Filipowicz R, Wang B, Wei G, Chen X, Roy AC, DuVall SL, Farrukh H, Habib AN, Bjordahl T, Simmons DL, Munger M, Stoddard G, Kohan DE, Greene T, Huang Y. A Randomized Controlled Trial of the Effects of Febuxostat Therapy on Adipokines and Markers of Kidney Fibrosis in Asymptomatic Hyperuricemic Patients With Diabetic Nephropathy. Can J Kidney Health Dis. 2016 Dec 5;3:2054358116675343. doi: 10.1177/2054358116675343. eCollection 2016.
PubMed 28270924
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Febuxostat on Adipokines and Kidney Disease in Diabetic Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT01350388
- Acronym / sponsor ID
- IRB_00044016
- Conditions
- Chronic Kidney Disease, Diabetes
- Keywords
- Chronic Kidney Disease, Diabetes, Febuxostat, Inflammation, Hyperuricemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- May 2011
- Primary completion
- Oct 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 9 May 2011 (estimated)
- Results
- Posted 3 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hyperuricemia is emerging as a risk factor for development of diabetes and metabolic syndrome. Recently, it was shown in in-vitro cell culture experiments that hyperuricemia induces redox-dependent signaling and oxidative stress in adipocytes. By targeting levels of uric acid with febuxostat it is hypothesized that the levels of oxidative stress in adipose tissue (obtained by fat biopsy) will decrease.
Primary aims of the study are to determine whether febuxostat therapy in overweight or obese, diabetic patients with stage 3 Chronic Kidney Disease (CKD) and high serum uric acid levels
- will affect adipose tissue concentrations of thiobarbituric acid reactive substance (TBARS), a marker of oxidative stress
- will affect adipose tissue expression and concentrations of adiponectin; and
- will affect urinary concentrations of transforming growth factor (TGF)- B1.
Detailed description
Hyperuricemia is highly prevalent in the US population and commonly clusters with obesity and metabolic syndrome. It remains controversial whether this reflects an epiphenomenon or connotes a causal role of hyperuricemia in metabolic syndrome. If indeed hyperuricemia plays a causal role in metabolic syndrome, it would be expected that hyperuricemia will impact on the molecular signals that mediate the effects of adiposity on inflammation and insulin resistance.
Adipokines, the protein hormones produced by the adipocytes, serve as the signals for the effects of adipocytes on insulin resistance, dyslipidemia, hypertension, inflammation and atherosclerosis. Adipokines include tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), plasminogen activator inhibitor (PAI-1), leptin, angiotensinogen and adiponectin. In obesity, the production of TNF-α, IL-6, PAI-1, leptin and angiotensinogen increases whereas the production of adiponectin decreases. Increased expression of pro-inflammatory TNF-α and IL-6 and decreased expression of anti-inflammatory adiponectin by adipocytes results in insulin resistance and inflammation.
As oxidative stress in adipose tissue is considered to play a critical role in dysregulation of adipokines production in obesity and that hyperuricemia induces oxidative stress in adipocytes, it is hypothesized that hyperuricemia alters adipose tissue production of adipokines; therefore, febuxostat therapy will decrease hyperuricemia and thereby, have beneficial effects on adipokine production by adipose tissue; the favorable effects on adipokine production by febuxostat therapy will result in decrease in plasma levels of markers of inflammation; and as a result of the above, urinary markers of kidney disease will improve.
Chronic Kidney Disease (CKD) patients with type 2 diabetes will be studies because this population has a high prevalence of hyperuricemia and likely represents a target population which might benefit from reduction of uric acid levels.
This is a placebo-controlled, double-blinded, randomized controlled trial to examine the effects of uric acid lowering with oral febuxostat on adipokines and markers of inflammation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Febuxostat | Active comparator | Drug: Febuxostat80 mg/day of febuxostat for 24 weeks |
| Placebo | Placebo comparator | Drug: Placebo1 placebo tablet per day for 24 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years
- BMI > 25 kg/m2
- type 2 diabetes
- serum uric acid ≥ 5.5 mg/dl in men and ≥ 4.6 mg/dl in women
- eGFR 30-60 mL/min/1.73m2
Key exclusion criteria (6 listed)
- History of gout
- concurrent use of azathioprine, mercaptopurine, theophylline, allopurinol, thiazolidinediones or warfarin
- concurrent use of metformin
- current antibiotic therapy
- pregnant women
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 |
|---|---|---|
| FebuxostatAlso: Uloric80 mg/day of febuxostat for 24 weeks | Drug | Febuxostat |
| Placebo1 placebo tablet per day for 24 weeks | Drug | Placebo |
Primary outcome
Change in Thiobarbituric Acid Reactive Substance (TBARS) Concentration in Adipose Tissue From Baseline to 24 Weeks
Time frame: Baseline and 24 weeks
The percent difference in thiobarbituric acid reactive substance (TBARS) concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Change in Adiponectin Concentration in Adipose Tissue From Baseline to 24 Weeks
Time frame: Baseline and 24 weeks
The percent difference in adiponectin concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Change in Urinary Concentrations of Transforming Growth Factor-beta1 (TGF-beta1) From Baseline to 24 Weeks
Time frame: Baseline and 24 weeks
The percent difference in TGF-beta1 concentration geometric mean values from baseline to 24 weeks was calculated for each arm
3 secondary outcomes
Change in Tumor Necrosis Factor-α (TNF-α) Concentration in Plasma From Baseline to 24 Weeks
Time frame: Baseline and 24 weeks
Change in Interleukin-6 (IL-6) Concentration in Plasma From Baseline to 24 Weeks
Time frame: Baseline and 24 weeks
Change in High Sensitivity C-Reactive Protein (hsCRP) Concentration in Plasma From Baseline to 24 Weeks
Time frame: Baseline and 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28270924Beddhu S, Filipowicz R, Wang B, Wei G, Chen X, Roy AC, DuVall SL, Farrukh H, Habib AN, Bjordahl T, Simmons DL, Munger M, Stoddard G, Kohan DE, Greene T, Huang Y. A Randomized Controlled Trial of the Effects of Febuxostat Therapy on Adipokines and Markers of Kidney Fibrosis in Asymptomatic Hyperuricemic Patients With Diabetic Nephropathy. Can J Kidney Health Dis. 2016 Dec 5;3:2054358116675343. doi: 10.1177/2054358116675343. eCollection 2016.
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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.
Srinivasan Beddhu, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Febuxostat in people with Chronic Kidney Disease and Diabetes, run by University of Utah 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 5 inclusion and 6 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 3 Oct 2016. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Thiobarbituric Acid Reactive Substance (TBARS) Concentration in Adipose Tissue From Baseline to 24 Weeks (time frame: Baseline and 24 weeks). The study lists 3 primary outcomes in all. 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 NCT01350388, which also lists 1 linked publication.
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 3 Oct 2016; AzTrials last refreshed its copy on 8 Nov 2026.