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

NCT ID: NCT03865407

Last Updated: 2021-05-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-10
• Study Completion Date: 2020-10-07

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.

Conditions

Hyperuricemia; Chronic Kidney Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Allopurinol

Intervention Type: DRUG

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

Standard of Care Control

The treatment arm will be compared to a standard of care arm.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Allopurinol

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cristin Kaspar, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HM20014698

Identifier Type: -

Identifier Source: org_study_id