Uric Acid Lowering Trial in Youth Onset T2D
- Conditions
- Diabetic Kidney DiseaseHyperuricemiaDiabetes Mellitus, Type 2Type2 DiabetesDiabetic NephropathiesDiabetesType 2 Diabetes MellitusDiabetes Complications
- Interventions
- Registration Number
- NCT03899883
- Lead Sponsor
- University of Colorado, Denver
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 10
- Men
- Ages 18-25
- Youth-onset T2D (diagnosis <21 years)
- serum uric acid ≥ 5 mg/dl
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pegloticase Pegloticase 8 MG/ML [Krystexxa] Single administration of pegloticase (8 mg IV in 250 mL 0.9% normal saline)
- Primary Outcome Measures
Name Time Method Cardiovascular Markers 5 min Measured by Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP)
Pulse Wave Velocity (PWV) 2 hours (x2 study visits) Measured by Aortic MRI renal MRI (4D Flow)
Wall Shear Stress (WSS) 2 hours (x2 study visits) Measured by Aortic MRI renal MRI (4D Flow)
Renal Blood Flow 1 hour (x2 study visits) Measured by 4D Flow renal MRI
Glomerular Filtration Rate 4 hours (x2 study visits) Measured by Iohexol Clearance in Plasma
Albumin Excretion Rate (AER) 4 hours (x2 study visits) Measured by albumin and creatinine concentrations in urine
- Secondary Outcome Measures
Name Time Method Calculated parameters of intrarenal hemodynamic function 1 hour Measured by using existing renal hemodynamic calculations
Change in serum uric acid (sUA) 1 hour Measured by baseline sUA compared to sUA one week later
Trial Locations
- Locations (1)
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States