Clinical trial NCT03899883: Uric Acid Lowering Trial in Youth Onset T2D
Official title: ULTRA-T2D Study: Uric Acid Lowering Trial in Youth Onset T2D
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Diabetic Kidney Disease
Hyperuricemia
Diabetes
Diabetes Mellitus, Type 2
Type2 Diabetes
Type 2 Diabetes Mellitus
Diabetic Nephropathies
Diabetes Complications
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2019-04-02
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 25
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Cardiovascular Markers
timeFrame: 5 min
measure: Pulse Wave Velocity (PWV)
timeFrame: 2 hours (x2 study visits)
measure: Wall Shear Stress (WSS)
timeFrame: 2 hours (x2 study visits)
measure: Renal Blood Flow
timeFrame: 1 hour (x2 study visits)
measure: Glomerular Filtration Rate
timeFrame: 4 hours (x2 study visits)
measure: Albumin Excretion Rate (AER)
timeFrame: 4 hours (x2 study visits)
Secondary outcomes:
measure: Calculated parameters of intrarenal hemodynamic function
timeFrame: 1 hour
measure: Change in serum uric acid (sUA)
timeFrame: 1 hour
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
References: