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Purpose

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

Eligibility

Eligible Ages
Between 18 Years and 25 Years
Eligible Sex
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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.

Recruiting Locations

Children's Hospital Colorado
Aurora, Colorado 80045
Contact:
Amy Rydin, MD
720-777-2560
amy.rydin@childrenscolorado.org

More Details

Status
Recruiting
Sponsor
University of Colorado, Denver

Study Contact

Amy Rydin, MD
720-777-2560
amy.rydin@childrenscolorado.org

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.