Uric Acid Lowering Trial in Youth Onset T2D (ULTRA-T2D)

ULTRA-T2D Study: Uric Acid Lowering Trial in Youth Onset T2D

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Diabetes; Diabetes Complications; Type 2 Diabetes Mellitus; Diabetic Kidney Disease; Diabetic Nephropathies; Type2 Diabetes; Hyperuricemia
• Intervention / Treatment: Drug: Pegloticase 8 MG/ML [Krystexxa]

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amy Rydin, MD; Phone Number: 720-777-2560; Email: amy.rydin@childrenscolorado.org
• Study Contact Backup: Name: Carissa Vinovskis, MS; Phone Number: 720-777-2660; Email: carissa.vinovskis@childrenscolorado.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Contact: Amy Rydin, MD; Phone Number: 720-777-2560; Email: amy.rydin@childrenscolorado.org
      • Contact: Carissa Vinovskis, MS; Phone Number: 720-777-2660; Email: carissa.vinovskis@childrenscolorado.org
      • Principal Investigator: Amy Rydin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pegloticase; Single administration of pegloticase (8 mg IV in 250 mL 0.9% normal saline)	Drug: Pegloticase 8 MG/ML [Krystexxa]; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculated parameters of intrarenal hemodynamic function	Measured by using existing renal hemodynamic calculations	1 hour
Change in serum uric acid (sUA)	Measured by baseline sUA compared to sUA one week later	1 hour

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2020
• Primary Completion (ANTICIPATED): June 30, 2023
• Study Completion (ANTICIPATED): June 30, 2023

Study Registration Dates

• First Submitted: March 28, 2019
• First Submitted That Met QC Criteria: March 29, 2019
• First Posted (ACTUAL): April 2, 2019

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Diabetic Nephropathies; Hyperuricemia; Diabetes Complications
• Other Study ID Numbers: 18-1700

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No