Clinical trial NCT03865407: Uric Acid Reduction as a Novel Treatment for Pediatric Chronic Kidney Disease
Official title: Uric Acid Reduction as a Novel Treatment for Pediatric Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hyperuricemia
Chronic Kidney Diseases
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2019-03-06
Enrollment: 17
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: eGFR Change
timeFrame: The difference in Cystatin C eGFR between baseline and 6 months will be measured
measure: eGFR Change
timeFrame: The difference in Creatinine eGFR between baseline and 6 months will be measured
Secondary outcomes:
measure: Serum Uric Acid Change
timeFrame: The difference in Serum Uric Acid between baseline and 6 months will be measured
measure: Systolic Blood Pressure
timeFrame: The difference in clinic systolic blood pressure between baseline and 6 months will be measured
measure: Diastolic Blood Pressure
timeFrame: The difference in clinic diastolic blood pressure between baseline and 6 months will be measured
Other outcomes:
measure: Serum High Sensitivity C-reactive Protein (Hs-CRP)
timeFrame: Serum hs-CRP will be measured at baseline and 6 months
measure: Interleukin 18
timeFrame: Serum interleukin 18 will be measured at baseline, 3 months, and 6 months
measure: Serum Nlrp3
timeFrame: Serum Nlrp3 will be measured at baseline, 3 months, and 6 months
measure: Urine Neutrophil Gelatinase-associated Lipocalin (NGAL)
timeFrame: Urine NGAL will be measured at baseline, 3 months, and 6 months
measure: Urine Endothelin-1 (ET-1)
timeFrame: Urine ET-1 will be measured at baseline, 3 months, and 6 months
measure: Urine Kidney Injury Molecule-1 (KIM-1)
timeFrame: Urine KIM-1 will be measured at baseline, 3 months, and 6 months
measure: Urine N-acetyl-Beta-D-Glucosaminidase (NAG)
timeFrame: Urine NAG will be measured at baseline, 3 months, and 6 months
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Cristin Kaspar, MD
role: PRINCIPAL_INVESTIGATOR
References: