- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03865407
Uric Acid Reduction as a Novel Treatment for Pediatric Chronic Kidney Disease
May 4, 2021 updated by: Virginia Commonwealth University
Aim 1. To determine the effect of Allopurinol treatment on renal function (glomerular filtration rate, GFR) in pediatric chronic kidney disease (CKD) patients with high uric acid levels (hyperuricemia).
Aim 2. Establish whether Allopurinol treatment reduces Nlrp3 inflammasome and renal injury biomarkers.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
Uric acid levels often rise when kidney function declines.
Historically, high uric acid has not been treated unless the uric acid crystallizes in the joint space and causes clinical gout disease, more typically seen in adults.
However, new research has shown that high uric acid levels are associated with the development of hypertension, inflammation, and both acute and chronic kidney injury.
Adult patients on renal dialysis who have hyperuricemia also have higher mortality rates.
In several adult and in one pediatric clinical trial of uric acid lowering therapy (with Allopurinol or Febuxostat), treatment has demonstrated a slower rate of renal function decline and improved blood pressure compared to placebo.
The pediatric trial was a 4-month placebo controlled trial of Allopurinol, and showed positive improvement in renal function and blood pressure, but did not adequately control for potential confounders in the outcome.
Two known confounders that influence renal function (glomerular filitration rate, GFR) in pediatric CKD are race and glomerular or non-glomerular disease etiology.
This study is designed to control for these confounders and establish whether Allopurinol for 6 months of treatment to a goal range of 3-5 mg/dL will improve renal function compared to standard of care.
The secondary outcome is to determine whether blood pressure is affected by the treatment and the magnitude of change of serum uric acid.
This study will also explore whether Allopurinol treatment alters activation of the Nlrp3 inflammasome or renal injury biomarkers.
Study Type
Interventional
Enrollment (Actual)
17
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Virginia
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Richmond, Virginia, United States, 23298
- Virginia Commonwealth University
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
2 years to 20 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Chronic Kidney Disease stage 1-5
- Hyperuricemic (UA >= 5.5 mg/dL)
Exclusion Criteria:
- Contraindication to Allopurinol
- Elevated baseline liver function tests
- Receiving acute or chronic dialysis
- Primary metabolic disorder
- Sickle cell disease
- Autosomal Dominant Polycystic Kidney Disease
- Cystinosis
- Bartter or Gitelman Disease
- Pregnant or nursing
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Allopurinol
Allopurinol will be administered to this treatment arm group for 6 months.
Participants will receive the lowest FDA recommended dose for weight, and will be titrated upwards to achieve the goal uric acid level of 3-5 mg/dL throughout the trial.
|
Allopurinol dosed to target uric acid levels of 3-5 mg/dL.
|
No Intervention: Standard of Care Control
The treatment arm will be compared to a standard of care arm.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
eGFR Change
Time Frame: The difference in Cystatin C eGFR between baseline and 6 months will be measured
|
Change in Cys-C eGFR over time
|
The difference in Cystatin C eGFR between baseline and 6 months will be measured
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eGFR Change
Time Frame: The difference in Creatinine eGFR between baseline and 6 months will be measured
|
Change in Creatinine eGFR over time
|
The difference in Creatinine eGFR between baseline and 6 months will be measured
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum Uric Acid Change
Time Frame: The difference in Serum Uric Acid between baseline and 6 months will be measured
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Change in Serum Uric Acid
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The difference in Serum Uric Acid between baseline and 6 months will be measured
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Systolic Blood Pressure
Time Frame: The difference in clinic systolic blood pressure between baseline and 6 months will be measured
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Change in systolic blood pressure
|
The difference in clinic systolic blood pressure between baseline and 6 months will be measured
|
Diastolic Blood Pressure
Time Frame: The difference in clinic diastolic blood pressure between baseline and 6 months will be measured
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Change in diastolic blood pressure
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The difference in clinic diastolic blood pressure between baseline and 6 months will be measured
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum High Sensitivity C-reactive Protein (Hs-CRP)
Time Frame: Serum hs-CRP will be measured at baseline and 6 months
|
Compare the mean difference of serum hs-CRP from baseline to 6 months between groups
|
Serum hs-CRP will be measured at baseline and 6 months
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Interleukin 18
Time Frame: Serum interleukin 18 will be measured at baseline, 3 months, and 6 months
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Change in interleukin 18
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Serum interleukin 18 will be measured at baseline, 3 months, and 6 months
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Serum Nlrp3
Time Frame: Serum Nlrp3 will be measured at baseline, 3 months, and 6 months
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Change in serum Nlrp3
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Serum Nlrp3 will be measured at baseline, 3 months, and 6 months
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Urine Neutrophil Gelatinase-associated Lipocalin (NGAL)
Time Frame: Urine NGAL will be measured at baseline, 3 months, and 6 months
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Change in urine NGAL
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Urine NGAL will be measured at baseline, 3 months, and 6 months
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Urine Endothelin-1 (ET-1)
Time Frame: Urine ET-1 will be measured at baseline, 3 months, and 6 months
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Change in urine ET-1
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Urine ET-1 will be measured at baseline, 3 months, and 6 months
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Urine Kidney Injury Molecule-1 (KIM-1)
Time Frame: Urine KIM-1 will be measured at baseline, 3 months, and 6 months
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Change in urine KIM-1
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Urine KIM-1 will be measured at baseline, 3 months, and 6 months
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Urine N-acetyl-Beta-D-Glucosaminidase (NAG)
Time Frame: Urine NAG will be measured at baseline, 3 months, and 6 months
|
Change in urine NAG
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Urine NAG will be measured at baseline, 3 months, and 6 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Cristin Kaspar, MD, Virginia Commonwealth University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 10, 2019
Primary Completion (Actual)
October 7, 2020
Study Completion (Actual)
October 7, 2020
Study Registration Dates
First Submitted
March 5, 2019
First Submitted That Met QC Criteria
March 5, 2019
First Posted (Actual)
March 6, 2019
Study Record Updates
Last Update Posted (Actual)
May 27, 2021
Last Update Submitted That Met QC Criteria
May 4, 2021
Last Verified
May 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Urologic Diseases
- Renal Insufficiency
- Kidney Diseases
- Renal Insufficiency, Chronic
- Hyperuricemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites
- Protective Agents
- Antioxidants
- Free Radical Scavengers
- Gout Suppressants
- Allopurinol
Other Study ID Numbers
- HM20014698
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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