Uric Acid Lowering Trial in Youth Onset T2D

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

Sponsors

Lead Sponsor: University of Colorado Denver School of Medicine Barbara Davis Center

Source University of Colorado Denver School of Medicine Barbara Davis Center
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.

Overall Status Recruiting
Start Date January 1, 2020
Completion Date December 31, 2020
Primary Completion Date May 31, 2020
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Cardiovascular Markers 5 min
Pulse Wave Velocity (PWV) 2 hours (x2 study visits)
Wall Shear Stress (WSS) 2 hours (x2 study visits)
Renal Blood Flow 1 hour (x2 study visits)
Glomerular Filtration Rate 4 hours (x2 study visits)
Albumin Excretion Rate (AER) 4 hours (x2 study visits)
Secondary Outcome
Measure Time Frame
Calculated parameters of intrarenal hemodynamic function 1 hour
Change in serum uric acid (sUA) 1 hour
Enrollment 10
Condition
Intervention

Intervention Type: Drug

Intervention Name: Pegloticase 8 MG/ML [Krystexxa]

Description: 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.

Arm Group Label: Pegloticase

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

Gender: Male

Gender Based: Yes

Minimum Age: 18 Years

Maximum Age: 25 Years

Healthy Volunteers: No

Overall Contact

Last Name: Amy Rydin, MD

Phone: 720-777-2560

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Investigator: Children's Hospital Colorado Amy Rydin, MD 720-777-2560 [email protected] Amy Rydin, MD Principal Investigator
Location Countries

United States

Verification Date

March 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Colorado Denver School of Medicine Barbara Davis Center

Investigator Full Name: Petter Bjornstad

Investigator Title: Assistant Professor; Department of Medicine, Division of Pediatrics & Nephrology

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Pegloticase

Type: Experimental

Description: Single administration of pegloticase (8 mg IV in 250 mL 0.9% normal saline)

Acronym ULTRA-T2D
Patient Data Undecided
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov