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Uric Acid Lowering Trial in Youth Onset T2D (ULTRA-T2D)

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ClinicalTrials.gov Identifier: NCT03899883
Recruitment Status : Recruiting
First Posted : April 2, 2019
Last Update Posted : November 4, 2020
Sponsor:
Information provided by (Responsible Party):
Petter Bjornstad, University of Colorado Denver School of Medicine Barbara Davis Center

Study Description
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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.


Condition or disease Intervention/treatment Phase
Diabetic Kidney Disease Hyperuricemia Diabetes Diabetes Mellitus, Type 2 Type2 Diabetes Type 2 Diabetes Mellitus Diabetic Nephropathies Diabetes Complications Drug: Pegloticase 8 MG/ML [Krystexxa] Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ULTRA-T2D Study: Uric Acid Lowering Trial in Youth Onset T2D
Actual Study Start Date : January 1, 2020
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : December 31, 2022

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Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. Cardiovascular Markers [ Time Frame: 5 min ]
    Measured by Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP)

  2. Pulse Wave Velocity (PWV) [ Time Frame: 2 hours (x2 study visits) ]
    Measured by Aortic MRI renal MRI (4D Flow)

  3. Wall Shear Stress (WSS) [ Time Frame: 2 hours (x2 study visits) ]
    Measured by Aortic MRI renal MRI (4D Flow)

  4. Renal Blood Flow [ Time Frame: 1 hour (x2 study visits) ]
    Measured by 4D Flow renal MRI

  5. Glomerular Filtration Rate [ Time Frame: 4 hours (x2 study visits) ]
    Measured by Iohexol Clearance in Plasma

  6. Albumin Excretion Rate (AER) [ Time Frame: 4 hours (x2 study visits) ]
    Measured by albumin and creatinine concentrations in urine


Secondary Outcome Measures :
  1. Calculated parameters of intrarenal hemodynamic function [ Time Frame: 1 hour ]
    Measured by using existing renal hemodynamic calculations

  2. Change in serum uric acid (sUA) [ Time Frame: 1 hour ]
    Measured by baseline sUA compared to sUA one week later


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 25 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03899883


Contacts
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Contact: Amy Rydin, MD 720-777-2560 amy.rydin@childrenscolorado.org
Contact: Carissa Vinovskis, MS 720-777-2660 carissa.vinovskis@childrenscolorado.org

Locations
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United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Amy Rydin, MD    720-777-2560    amy.rydin@childrenscolorado.org   
Contact: Carissa Vinovskis, MS    720-777-2660    carissa.vinovskis@childrenscolorado.org   
Principal Investigator: Amy Rydin, MD         
Sponsors and Collaborators
University of Colorado Denver School of Medicine Barbara Davis Center
More Information
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Responsible Party: Petter Bjornstad, Assistant Professor; Department of Medicine, Division of Pediatrics & Nephrology, University of Colorado Denver School of Medicine Barbara Davis Center
ClinicalTrials.gov Identifier: NCT03899883    
Other Study ID Numbers: 18-1700
First Posted: April 2, 2019    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Diseases
Diabetic Nephropathies
Diabetes Mellitus
Diabetes Mellitus, Type 2
Diabetes Complications
Hyperuricemia
 Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Pathologic Processes