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current studies

Our studies assess several related research questions from different angles, as we comprehensively evaluate established and novel markers of kidney function and early predictors of DKD and CVD in youth and adults with Type 1 and Type 2 Diabetes

Non-industry studies:

+ 1. Renal-HEIR

Full Title: Renal HEIR Study: Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes Study

Principal Investigator: Petter Bjornstad, M.D.

Co-investigators: Kristen J. Nadeau, M.D., M.S., Richard J. Johnson, M.D., Lorna Browne, M.D., Pottumarthi V Prasad, Ph.D., David Cherney, M.D., Ph.D., Robert G. Nelson, M.D., Ph.D., Patrica Ladd, M.D., Roger Harned, M.D., Kalie Tommerdahl, M.D.

A better understanding of the pathophysiology underlying hyperfiltration and its relationship with insulin resistance is critical to inform development of new therapeutics. The investigators' overarching hypotheses are that: 1) hyperfiltration in youth-onset T2D is associated with changes in intrarenal hemodynamics, resulting in increased renal oxygen demand, 2) the demand is unmet by the inefficient fuel profile associated with IR (decreased glucose oxidation and increase free fatty acid [FFA] oxidation), resulting in renal hypoxia and ultimately renal damage. To address these hypotheses, the investigators will measure peripheral insulin sensitivity, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and renal oxygenation and perfusion by MRI in youth (12-21 years of age) with T2D (n=60), obesity (n=20) and in lean (n=20) controls.

Sponsor: NIH/NIDDK, Boettcher Foundation, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 2. IMPROVE-T2D

Full Title: IMPROVE-T2D Study: Impact of Metabolic Surgery on Pancreatic, Renal and CardiOVascular HEalth in Youth with Type 2 Diabetes

Principal Investigators: Petter Bjornstad, M.D., Kristen Nadeau, M.D., M.S., and Thomas Inge, M.D., Ph.D.

Co-Investigators: Alexander Barker, Ph.D., Laura Pyle, Ph.D., Kalie Tommerdahl, M.D., Lorna Browne, M.D., Pottumarthi V Prasad, Ph.D., David Cherney, M.D., Ph.D., Robert G. Nelson, M.D. Ph.D., Megan Kelsey, M.D., M.S., Melanie Cree Green, M.D., Ph.D., Michal Schafer, M.S., Philip S. Zeitler, M.D., Ph.D., Patrica Ladd, M.D., Roger Harned, M.D.

A better understanding of the effects of bariatric surgery on pancreatic function, intrarenal hemodynamics, renal oxygenation and cardiovascular function is critical to help define mechanisms of surgical benefits, to help identify potential novel future non-surgical approaches to prevent pancreatic failure, DKD and CVD. Our overarching hypotheses are that: 1) Youth-onset T2D is associated with IR, pancreatic dysfunction, intrarenal hemodynamic dysfunction, and cardiovascular dysfunction which improve with bariatric surgery, 2) The early effect of bariatric surgery on cardiorenal health is mediated by improvement in IR and weight loss. To address these hypotheses, we will measure cardio-renal health, in addition to aortic stiffness, β-cell function and insulin sensitivity and central adiposity in youth-onset T2D (n=15) before and 3 and 12 months after vertical sleeve gastrectomy (VSG).

Sponsor: NIH/NIDDK, American Heart Association, Children’s Hospital Colorado Research Institute, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 3. CROCODILE

Full Title: CROCODILE Study: Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance

Principal Investigators: Petter Bjornstad, M.D.

Co-Investigators: Pottumarthi V Prasad, Ph.D, Laura Pyle, Ph.D., Kalie Tommerdahl, M.D., Kristen Nadeau, M.D., Lynette Driscoll, PA-C, Denis Blondin, Ph.D., Gabriel Richard, Ph.D., Viral Shah, M.D., Michel Chonchol, M.D., Patricia Ladd, M.D., Roger Harned, M.D., David Cherney, M.D., Ph.D., Daniel van Raalte, M.D., Ph.D., Robert G. Nelson, M.D., Ph.D.

Cross-sectional study integrating gold-standard renal physiology methods (iohexol and p-aminohippurate clearance), multimodal and multiparametric functional imaging of the kidney (MRI and PET/CT), as well as research kidney biopsies and hyperinsulinemic-euglycemic clamps to determine the morphometric, molecular and metabolic determinants of early kidney dysfunction in young adults with T1D.

Sponsor: JDRF, NIH/NIDDK DRC, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 4. PENGUIN

Full Title: PENGUIN Study: PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD

Principal Investigators: Petter Bjornstad, M.D. and Berenice Gitomer, Ph.D.

Co-Investigators: Kristen Nowak, Ph.D., Michel Chonchol, M.D., Tim Kline, Ph.D., Denis Blondin, Ph.D., Gabriel Richard, Ph.D., Pottumarthi V Prasad, Ph.D, Laura Pyle, Ph.D., Kalie Tommerdahl, M.D.

Cross-sectional study integrating gold-standard renal physiology methods (iohexol and p-aminohippurate clearance), multimodal and multiparametric functional imaging of the kidney (MRI and PET/CT), as well as hyperinsulinemic-euglycemic clamps to determine the metabolic determinants of cyst burden in adults with autosomal polycystic kidney disease (ADPKD). Additionally, this study seeks to develop a method to quantify metabolically active kidney tissue in ADPKD.

Sponsor: NIH/NIDDK, CU-PKD Pilot Funds, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 5. PANTHER

Full Title: PANTHER Study: Puberty, Diabetes, and the Kidneys, When Eustress Becomes Distress

Principal Investigators: Petter Bjornstad, M.D.

Co-Investigators: Alexander Barker, Ph.D., Laura Pyle, Ph.D., Kalie Tommerdahl, M.D., Lorna Browne, M.D., Pottumarthi V Prasad, Ph.D., Ph.D., Robert G. Nelson, M.D. Ph.D., Megan Kelsey, M.D., M.S., Kristen Nadeau, M.D., Lynette Driscoll, PA-C.

Accelerated longitudinal study in 100 adolescents to evaluate the effects of puberty on kidney structure and function by leveraging gold-standard renal clearance procedures (iohexol, p-aminohippurate and dextran clearance), multiparametric MRI, metabolomics and proteomics, as well as comprehensive metabolic and endocrine assessments and biochemical measurements.

Sponsor: NIH/NIDDK, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 6. ATTEMPT

Full Title: ATTEMPT trial: Adolescent Type 1 Diabetes Treatment With SGLT2i for hyperglycEMia & hyPerfilTration Trial

Principal Investigators: Farid Mahmud, M.D.

Site-Principal Investigator: Petter Bjornstad, M.D.

Co-Investigators: Kalie Tommerdahl, M.D., Patricia Ladd, M.D., Pottumarthi V Prasad, Ph.D., Robert G. Nelson, M.D. Ph.D., Lynette Driscoll, PA-C., Roger Harned, M.D.

Placebo-controlled randomized control trial evaluating the cardio-renal effects of 16 weeks of dapagliflozin in 100 adolescents and young adults with T1D. (Canadian sites enroll adolescents, Colorado site only enrolls young adults)

Sponsor: JDRF, CIHR, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 7. PANDA

Full Title: Pathogenesis of Kidney Disease in Type 1 Diabetes: a Modern Kidney Biopsy Cohort

Principal Investigators: Petter Bjornstad, M.D. and Ian de Boer, M.D., M.S.

Co-Investigators at University of Colorado: Kalie Tommerdahl, M.D., Patricia Ladd, M.D., Pottumarthi V Prasad, Ph.D., Robert G. Nelson, M.D. Ph.D., Carissa Vinovskis, M.D., Susan Gross, R.D., Lynette Driscoll, PA-C.

Co-Investigators at University of Washington: Irl Hirsch, M.D., Ernie Ayers, MS, Nichole Ehrhardt, M.D., Nayan Arora, M.D., Ashley Jefferson, M.D., Ramya Ravichandran, M.D.

Co-Investigators at University of Michigan: Matthias Kretzler, M.D., Jeff Hodgin, M.D., Ph.D.

Collaborator: Luiza Caramori, M.D.

Modern kidney biopsy cohort of 100 adults with T1D across the spectrum of diabetes duration. Participants will undergo research kidney biopsies as well as multiparametric kidney MRI, DXA and annual blood and urine collections.

Sponsor: NIH/NIDDK

+ 8. COFFEE [COMPLETED]

Full Title: COFFEE Study: Evaluation of Coffee Therapy for Improvement of Renal Oxygenation

Principal Investigators: Petter Bjornstad, M.D. and Chirag Parikh, M.D., Ph.D.

Co-Investigators: Pottumarthi V Prasad, Ph.D, Laura Pyle, Ph.D., Kalie Tommerdahl, M.D.

Pilot and feasibility study evaluating the effects of 7 days of cold brew coffee on kidney oxygenation and intraglomerular hemodynamic function in adolescents with type 1 diabetes.

Sponsor: Johns Hopkins University, JDRF, Colorado Clinical and Translational Sciences Institute (CCTSI) Publication: https://pubmed.ncbi.nlm.nih.gov/35812290/ and https://pubmed.ncbi.nlm.nih.gov/35812301/

+ 9. CASPER [COMPLETED]

Full Title: CASPER Study: Copeptin in Adolescent Participants with Type 1 Diabetes and Early Renal Hemodynamic Function

Principal Investigators: Petter Bjornstad, M.D.

Co-Investigators: Pottumarthi V Prasad, Ph.D, Laura Pyle, Ph.D., Kristen Nadeau, M.D., M.S., Marian Rewers, M.D., Ph.D., David Z. Cherney, M.D., Ph.D., Bruce A. Perkins, M.D., M.P.H.

Animal research demonstrates that arginine vasopressin (AVP) acts directly at the V2 receptor (V2R) to modify intrarenal hemodynamic function, but also indirectly by activating RAAS (Tamaki et al. Kidney Int 1996). Our preliminary data suggest that elevated copeptin, a marker of AVP, predicts DKD in T1D adults, independently of other risk factors (Bjornstad et al. J Diabetes Complications 2016 and 2017). However, no human studies to date have examined how copeptin relates to intrarenal hemodynamic function in early DKD in T1D. A better understanding of this relationship is critical to inform development of new therapies targeting the AVP system in T1D. Accordingly, in this study, we propose to define the relationship between copeptin and intrarenal hemodynamics in early stages of DKD, by studying youth aged 12-21 years with T1D duration < 10 years. We will compare our findings with mechanistic data already collected in adults with longstanding T1D (≥ 50 years), with and without DKD (DKD and DKD Resistors) from the JDRF-funded Canadian Study of Longevity in Diabetes.

Sponsor: JDRF, NIDDK/DiaComp, Colorado Clinical and Translational Sciences Institute (CCTSI) Publication: https://pubmed.ncbi.nlm.nih.gov/32737116/ and https://pubmed.ncbi.nlm.nih.gov/35286453/

+ 10. DKA Study [COMPLETED]

Full Title: Diabetic Kidney Alarm Study

**Principal Investigators: Petter Bjornstad, M.D.

Co-Investigators: Carlos Roncal, M.S., Kristen Nadeau, M.D., M.S., Richard J. Johnson, M.D., David M. Maahs, M.D., Ph.D. and Arleta Rewers, M.D., Ph.D.

The overarching goals of this study are to determine whether tubular dysfunction and injury is present in new onset diabetic ketoacidosis (age 3-18), whether it is reversible and whether it is related to uricosuria and copeptin. The investigators propose to study a cohort of youth (ages 3-18, n=40) with new onset T1D who have serum and urine collection at DKA diagnosis and 3-month follow-up.

Sponsor: Thrasher Research Fund, JDRF-ISPAD Research Fellowship, Diabetes Guild, Colorado Clinical and Translational Sciences Institute (CCTSI) Publication: https://pubmed.ncbi.nlm.nih.gov/34435718/

+ 11. Renal blood flow Study [COMPLETED]

Full Title: Renal blood flow and glomerular filtration rate by phase-contrast MRI

NCT (if applicable): N/A

Principal Investigators: Petter Bjornstad, M.D. and Michal Schafer, M.S., Ph.D. Co-investigators: Alexander Barker, Ph.D.; Lorna Browne, M.D., Kristen J. Nadeau, M.D. M.S.; Amy Keating, M.D.; Michael Verneris, M.D.; Hesham Eissa, M.D.; Roger Giller, M.D.; Alisa Lee Sherick, M.D.; Chris McKinney, M.D.; Ralph Quinones, M.D.**

To improve the availability, convenience and safety of ERPF and GFR assessments in youth, we propose adding phase-contrast (PC) MRI in 10 pediatric patients who are status pre-bone marrow transplant (BMT) and scheduled for iothalamate renography. We hypothesize that ERPF quantified by PC-MRI will strongly correlate with GFR derived by iothalamate clearance, and that GFR calculated by PC-MRI (GFR-MRI) will strongly correlate with GFR by iothalamate clearance. Our proposed study is significant in that a major gap in the field of kidney disease surveillance and research is to easily, safely and economically measure ERPF and GFR.

Sponsor: Children’s Hospital Colorado Radiology Funds, Colorado Clinical and Translational Sciences Institute (CCTSI) Publication: Data presented at ISMRM. Manuscript under preparation.

+ 12. Alk-UA Study [COMPLETED]

Full Title: Effect of Urinary Alkalinization on Urine Uric Acid Precipitation and Crystallization in Adults with Type 1 Diabetes

Principal Investigators: Petter Bjornstad, M.D.

Co-Investigators: Satish Garg, M.D., Marian Rewers, M.D., Ph.D., Janet K. Snell-Bergeon, Ph.D., David Maahs, M.D., Ph.D., Viral Shah, M.D. Sam Ellis, Pharm.D, Carlos Roncal, M.S., Richard J. Johnson, M.D.

Uricosuria and uric acid crystallization are increasingly recognized risk factors for diabetic tubulopathy. This pilot clinical trial aimed to determine the acute effect of urinary alkalinization using oral sodium bicarbonate (NaHCO3) on uric acid crystals in adults with T1D.

Sponsor: Colorado Clinical and Translational Sciences Institute (CCTSI) Publication: https://www.ncbi.nlm.nih.gov/pubmed/29498467

Industry studies:

+ 1. REMODEL

Full Title: REMODEL: A Research Study to Find Out How Semaglutide Works in the Kidneys Compared to Placebo, in People With Type 2 Diabetes and Chronic Kidney Disease

+ 2. DAPA-SALT

Full Title: DAPASALT: An Open Label, Phase IV, Mechanistic Study to Evaluate the Natriuretic Effect of 2-Week Dapagliflozin treatment in Type 2 Diabetes Mellitus Patients with Impaired Renal Function

+ 3. ZODIAC

Full Title: ZODIAC: Zibotentan and Dapagliflozin in Patients With Type 2 Diabetes and Elevated Albuminuria

+ 4. Renal Mechanism of SGLT2 Inhibition

Full Title: Renal Mechanism of SGLT2 Inhibition

+ 5. DESIGN

Full Title: Dietary Sodium Intake effects on ertugliflozin-induced changes in GFR, renal oxygenation and systemic hemodynamics: the DESIGN study, a randomized, placebo-controlled, cross-over study with ertugliflozin in people with type 2 diabetes