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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03899883
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 40.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Kidney Disease; Hyperuricemia; Diabetes; Diabetes Mellitus, Type 2; Type2 Diabetes; Type 2 Diabetes Mellitus; Diabetic Nephropathies; Diabetes Complications	Drug: Pegloticase 8 MG/ML [Krystexxa]	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ULTRA-T2D Study: Uric Acid Lowering Trial in Youth Onset T2D
• Actual Study Start Date: Jan 1, 2020
• Anticipated Primary Completion Date: May 31, 2023
• Anticipated Study Completion Date: May 31, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Cardiovascular Markers [5 min]

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

2. Pulse Wave Velocity (PWV) [2 hours (x2 study visits)]

   Measured by Aortic MRI renal MRI (4D Flow)

3. Wall Shear Stress (WSS) [2 hours (x2 study visits)]

   Measured by Aortic MRI renal MRI (4D Flow)

4. Renal Blood Flow [1 hour (x2 study visits)]

   Measured by 4D Flow renal MRI

5. Glomerular Filtration Rate [4 hours (x2 study visits)]

   Measured by Iohexol Clearance in Plasma

6. Albumin Excretion Rate (AER) [4 hours (x2 study visits)]

   Measured by albumin and creatinine concentrations in urine

Secondary Outcome Measures

1. Calculated parameters of intrarenal hemodynamic function [1 hour]

   Measured by using existing renal hemodynamic calculations

2. Change in serum uric acid (sUA) [1 hour]

   Measured by baseline sUA compared to sUA one week later

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 25 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Colorado	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03899883
• Other Study ID Numbers: 18-1700
• First Posted: Apr 2, 2019
• Last Update Posted: Feb 17, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Kidney Diseases; Diabetic Nephropathies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Complications; Hyperuricemia

Study Results

No Results Posted as of Feb 17, 2022