Uric Acid Reduction as a Novel Treatment for Pediatric Chronic Kidney Disease

Chronic Kidney Diseases Clinical Trial

Official title:

Uric Acid Reduction as a Novel Treatment for Pediatric Chronic Kidney Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03865407
• Other study ID #: HM20014698
• Status: Terminated
• Phase: Phase 2
• Start date: March 10, 2019
• Est. completion date: October 7, 2020

Study information

• Verified date: May 2021
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: October 7, 2020
• Est. primary completion date: October 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 20 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Hyperuricemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Allopurinol
Allopurinol dosed to target uric acid levels of 3-5 mg/dL.

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Virginia Commonwealth University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum High Sensitivity C-reactive Protein (Hs-CRP)	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
Other	Interleukin 18	Change in interleukin 18	Serum interleukin 18 will be measured at baseline, 3 months, and 6 months
Other	Serum Nlrp3	Change in serum Nlrp3	Serum Nlrp3 will be measured at baseline, 3 months, and 6 months
Other	Urine Neutrophil Gelatinase-associated Lipocalin (NGAL)	Change in urine NGAL	Urine NGAL will be measured at baseline, 3 months, and 6 months
Other	Urine Endothelin-1 (ET-1)	Change in urine ET-1	Urine ET-1 will be measured at baseline, 3 months, and 6 months
Other	Urine Kidney Injury Molecule-1 (KIM-1)	Change in urine KIM-1	Urine KIM-1 will be measured at baseline, 3 months, and 6 months
Other	Urine N-acetyl-Beta-D-Glucosaminidase (NAG)	Change in urine NAG	Urine NAG will be measured at baseline, 3 months, and 6 months
Primary	eGFR Change	Change in Cys-C eGFR over time	The difference in Cystatin C eGFR between baseline and 6 months will be measured
Primary	eGFR Change	Change in Creatinine eGFR over time	The difference in Creatinine eGFR between baseline and 6 months will be measured
Secondary	Serum Uric Acid Change	Change in Serum Uric Acid	The difference in Serum Uric Acid between baseline and 6 months will be measured
Secondary	Systolic Blood Pressure	Change in systolic blood pressure	The difference in clinic systolic blood pressure between baseline and 6 months will be measured
Secondary	Diastolic Blood Pressure	Change in diastolic blood pressure	The difference in clinic diastolic blood pressure between baseline and 6 months will be measured