Clinical trial NCT05530356: Renal Hemodynamics, Energetics and Insulin Resistance: A Follow-up Study
Official title: Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes: A Follow-up Study
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Type 2 Diabetes
Diabetes Type 2
Diabetic Nephropathies
Nephropathy
Obesity
Adolescent Obesity
Diabetic Kidney Disease
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2022-09-07
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Maximum age (years): 26
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Population to be enrolled will be comprised of obese youth with and without T2D and lean controls who were previously enrolled in the Renal-HEIR (#16-1752) study.

Brief summary: The current protocol plans to enroll participants with youth-onset Type 2 Diabetes (T2D) as well as obese and lean controls from the Renal-HEIR - Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes Study (n=100) \[COMIRB #16-1752\] in a prospective investigation that seeks to 1) define the changes in kidney function by gold standard techniques and energetics by functional Magnetic Resonance Imaging (MRI) in adolescents with and without T2D as they transition to young adulthood; 2) quantify kidney oxidative metabolism by 11C-acetate Positron Emission Tomography (PET) in a subset of participants who are ≥18 years of age with youth-onset T2D and/or obesity; 3) determine peripheral arterial stiffness by SphygmoCor. Mechanistic insight will be provided by transcriptomic analyses of repeat biopsies 3-years after their initial biopsy for eligible participants with youth-onset T2D, as well as molecular analysis of tissue obtained from J-wire endovascular biopsies. This study will also leverage this well-characterized cohort of youths to define youth-onset T2D-related changes in brain morphology and function by structural MRI and resting-state functional MRI and through the assessment of cognitive function (fluid and crystallized intelligence) using the NIH Toolbox Cognitive Battery (NIHTB-CB), as an exploratory objective. All enrollees in Renal-HEIR have consented to be contacted for future research opportunities.


Eligibility criteria: Inclusion Criteria:

* Obese youth with and without Type 2 Diabetes + lean controls who were previously enrolled in the Renal HEIR Study
* Participants who will undergo a PET Scan: ≥ 18 years

Exclusion Criteria:

* Anemia
* Seafood, iodine, or penicillin allergy
* Pregnancy
* MRI Scanning contraindications (claustrophobia, implantable devices, \>550 lbs)
* History of bleeding or clotting disorders, thrombocytopenia, warfarin and/or heparin use
* Taking sulfonamides, procaine, thiazolsulfone or probenecid

Primary outcomes:
measure: Effective Renal Plasma Flow (ERPF)
timeFrame: 4 Hours
measure: Glomerular Filtration Rate
timeFrame: 4 Hours
measure: Glomerular Size Selectivity
timeFrame: 4 hours
measure: Renal Oxygen Availability
timeFrame: 1 hour
measure: Renal Perfusion
timeFrame: 1 hour
measure: 11-C Acetate Tracer Uptake
timeFrame: 1 Hour
measure: Renal Oxidative Metabolism
timeFrame: 1 Hour
measure: Blood Volume Fraction
timeFrame: 1 Hour
measure: Glomerular Basement Membrane Width
timeFrame: 1 Hour
measure: Mesangial Expansion
timeFrame: 1 Hour
measure: Interstitial Fibrosis
timeFrame: 1 Hour
measure: Renal Arteriosclerosis
timeFrame: 1 Hour
measure: Spatial Transcriptomics
timeFrame: 1 Hour
measure: Spatial Metabolomics
timeFrame: 1 Hour
Secondary outcomes:
measure: Pulse Wave Velocity between Carotid and Femoral Artery
timeFrame: 10 minutes
measure: Whole brain gray matter volume
timeFrame: 1 Hour
measure: Whole brain cortical thickness
timeFrame: 1 Hour
measure: Whole brain resting-state network connectivity
timeFrame: 1 Hour
measure: Age-corrected composite fluid cognition score
timeFrame: 1 Hour
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
affiliation: Children's Hospital Colorado
name: Petter Bjornstad, MD
role: PRINCIPAL_INVESTIGATOR
References: