Uric Acid Lowering Trial in Youth Onset T2D

NCT03899883 | Unknown Phase 2 FDA Drug

• 1 other identifier: 18-1700
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Adolescents and young adults with youth-onset type 2 diabetes (T2D) are disproportionally impacted by hyperuricemia compared to non-diabetic peers and youth with type 1 diabetes (T1D). In fact, 50% of males with youth-onset T2D have serum uric acid (SUA) greater than 6.8 mg/dl. The investigators also recently demonstrated that higher SUA conferred greater odds of developing hypertension and diabetic kidney disease (DKD) in youth with T2D over 7 years follow-up. Elevated SUA is thought to lead to cardiovascular disease (CVD) and DKD by inflammation, mitochondrial dysfunction and deleterious effects on nephron mass. While there are studies demonstrating beneficial effects of uric acid (UA) lowering on vascular health in the general population, there are no studies in youth-onset T2D. Youth-onset T2D carries a greater risk of DKD and CVD compared to adult-onset T2D and T1D. Accordingly, a clinical trial evaluating UA lowering therapies is needed in youth-onset T2D. Krystexxa (pegloticase), a uricase, effectively lowers SUA and therefore holds promise as a novel therapy to impede the development of CVD and DKD in youth-onset T2D. This proposal describes a pilot and feasibility trial evaluating the effect of UA lowering by pegloticase on markers of CVD and DKD in ten (n=10) youth aged 18-25 with youth-onset T2D (diagnosed \<21 years of age) over 7 days. The overarching hypothesis is that pegloticase improves marker of cardiorenal health by lowering UA.

Conditions

Diabetic Kidney Disease; Hyperuricemia; Diabetes; Diabetes Mellitus, Type 2; Type2 Diabetes; Type 2 Diabetes Mellitus; Diabetic Nephropathies; Diabetes Complications

Outcome Measures

Primary Outcomes (6)

• Cardiovascular Markers

  Measured by Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP)

  5 min

• Pulse Wave Velocity (PWV)

  Measured by Aortic MRI renal MRI (4D Flow)

  2 hours (x2 study visits)

• Wall Shear Stress (WSS)

  Measured by Aortic MRI renal MRI (4D Flow)

  2 hours (x2 study visits)

• Renal Blood Flow

  Measured by 4D Flow renal MRI

  1 hour (x2 study visits)

• Glomerular Filtration Rate

  Measured by Iohexol Clearance in Plasma

  4 hours (x2 study visits)

• Albumin Excretion Rate (AER)

  Measured by albumin and creatinine concentrations in urine

  4 hours (x2 study visits)

Secondary Outcomes (2)

• Calculated parameters of intrarenal hemodynamic function

  1 hour

• Change in serum uric acid (sUA)

  1 hour

Study Arms (1)

Pegloticase

EXPERIMENTAL

Single administration of pegloticase (8 mg IV in 250 mL 0.9% normal saline)

Drug: Pegloticase 8 MG/ML [Krystexxa]

Interventions

Pegloticase 8 MG/ML [Krystexxa] DRUG

One time dosing of pegloticase will be administered. Participants will receive an infusion of pegloticase over two hours in the outpatient clinical and translational research center (CTRC) at Children's Hospital Colorado, and will be monitored after infusion.

Pegloticase

Eligibility Criteria

• Age: 18 Years - 25 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men
• Ages 18-25
• Youth-onset T2D (diagnosis \<21 years)
• serum uric acid ≥ 5 mg/dl

You may not qualify if:

• Glucose-6-phosphate (G6P) deficiency
• Allergies to seafood or iodine
• MRI contraindications (severe claustrophobia, non-MRI compatible implantable devices, weight ≥ 450 lbs)
• HbA1C ≥ 12%
• Recent (1 month prior) diagnosis of diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemia
• Congestive heart failure
• History of multiple and/or severe allergies or anaphylactic reactions
• Uric acid lowering medications (ie: allopurinol, febuxostat)
• Pegvisomant, pegvaliase, peginterferon alfa 2b, peginterferon alfa 2a, pegfilgrastim, pegaspargase, pegaptanib, pegademase and certolizumab pegol
• Participation in another investigational study within 2 weeks prior to study

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Diabetic Nephropathies; Hyperuricemia; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Complications

Interventions

Pegloticase

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Amy Rydin, MD

CONTACT

720-777-2560; amy.rydin@childrenscolorado.org

Carissa Vinovskis, MS

CONTACT

720-777-2660; carissa.vinovskis@childrenscolorado.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: April 2, 2019
• Study Start: January 1, 2020
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: February 9, 2023

Record last verified: 2023-02

Locations

US (1)