Diabetes, Diabetes Complications, Diabetes Mellitus, Type 2, Diabetic Kidney Disease, Diabetic Nephropathies, Hyperuricemia, Type2 Diabetes, Type 2 Diabetes Mellitus
Conditions
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.
Interventions
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.
Sponsors
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 25 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | Baseline and 1 week post treatment | Systolic blood pressure measured by sphygmomanometer |
| Diastolic Blood Pressure | Baseline and 1 week post treatment | Diastolic blood pressure measured by sphygmomanometer |
| Mean Arterial Pressure | Baseline and 1 week post treatment | Mean arterial pressure measured by sphygmomanometer |
| Pulse Wave Velocity (PWV) | Baseline and 1 week post treatment | Measured by Aortic MRI renal MRI (4D Flow) |
| Wall Shear Stress (WSS) | Baseline and 1 week post treatment | Measured by Aortic MRI renal MRI (4D Flow) |
| Renal Blood Flow | Baseline and 1 week post treatment | Measured by 4D Flow renal MRI |
| Glomerular Filtration Rate | Baseline and 1 week post treatment | Measured by Iohexol Clearance in Plasma |
| Urine Albumin-creatinine Ratio | Baseline and 1 week post treatment | Measured by albumin and creatinine concentrations in urine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Uric Acid (sUA) | Baseline and 1 week post treatment | Measured by baseline sUA compared to sUA one week later |
Countries
United States
Participant flow
Recruitment details
Recruitment over 2-year study period (study start through completion of N=10 enrollment), targeting up to 14 men aged 18-35 with youth-onset T2D (diagnosis ≤ 25 yrs) and SUA ≥5 mg/dL. Participants are recruited from three clinical sites at the University of Colorado Anschutz Medical Campus: the Barbara Davis Center for Childhood Diabetes, the adult diabetes clinic at University of Colorado Hospital, and the pediatric T2D clinic at Children's Hospital Colorado.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 22 Years STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Mean arterial pressure | 98 mmHg STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 5 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
None listed