Uric Acid Lowering Trial in Youth Onset T2D

Diabetes Mellitus, Type 2 Clinical Trial

— ULTRA-T2D  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03899883
• Other study ID #: 18-1700
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2020
• Est. completion date: June 30, 2023

Study information

• Verified date: February 2023
• Source: University of Colorado, Denver
• Contact: Amy Rydin, MD
• Phone: 720-777-2560
• Email: amy.rydin[@]childrenscolorado.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 25 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiovascular Markers	Measured by Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP)	5 min
Primary	Pulse Wave Velocity (PWV)	Measured by Aortic MRI renal MRI (4D Flow)	2 hours (x2 study visits)
Primary	Wall Shear Stress (WSS)	Measured by Aortic MRI renal MRI (4D Flow)	2 hours (x2 study visits)
Primary	Renal Blood Flow	Measured by 4D Flow renal MRI	1 hour (x2 study visits)
Primary	Glomerular Filtration Rate	Measured by Iohexol Clearance in Plasma	4 hours (x2 study visits)
Primary	Albumin Excretion Rate (AER)	Measured by albumin and creatinine concentrations in urine	4 hours (x2 study visits)
Secondary	Calculated parameters of intrarenal hemodynamic function	Measured by using existing renal hemodynamic calculations	1 hour
Secondary	Change in serum uric acid (sUA)	Measured by baseline sUA compared to sUA one week later	1 hour