Clinical trial NCT03618420: Copeptin in Adolescent Participants With Type 1 Diabetes and Early Renal Hemodynamic Function
Official title: CASPER Study: Copeptin in Adolescent Participants With Type 1 Diabetes and Early Renal Hemodynamic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus, Type 1
Nephropathy
Diabetic Nephropathies
Juvenile Diabetes
Diabetes Mellitus Complication
Autoimmune Diabetes
Type 1 Diabetes Mellitus
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2018-08-07
Enrollment: 50
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All study participants will receive the same intervention.
Primary purpose: DIAGNOSTIC

Brief summary: Over 1.25 million Americans have type 1 diabetes (T1D), increasing risk for early death from cardiorenal disease. The strongest risk factor for cardiovascular disease (CVD) and mortality in T1D is diabetic kidney disease (DKD). Current treatments, such as control of hyperglycemia and hypertension, are beneficial, but only partially protect against DKD.

Hyperfiltration is common in youth with T1D, and predicts progressive DKD. Hyperfiltration is also associated with early changes in intrarenal hemodynamic function, including increased renal plasma flow (RPF) and glomerular pressure. Intrarenal hemodynamic function is strongly influenced by the renin-angiotensin-aldosterone system (RAAS), which is also considered a key player in the pathogenesis of DKD. Preliminary data demonstrate differences in intrarenal hemodynamic function and RAAS activation in early and advanced DKD in T1D. However, the pathophysiology contributing to the differences observed in RAAS activation and intrarenal hemodynamic function in T1D are poorly defined Animal research demonstrates that arginine vasopressin (AVP) acts directly to modify intrarenal hemodynamic function, but also indirectly by activating RAAS. Preliminary data suggest that elevated copeptin, a marker of AVP, which predicts DKD in T1D adults, independently of other risk factors. 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, the investigators propose to define the relationship between copeptin and intrarenal hemodynamics in early stages of DKD, by studying copeptin levels, renal plasma flow, and glomerular filtration in youth (n=50) aged 12-21 y with T1D duration \< 10 y.


Eligibility criteria: Inclusion Criteria:

* Antibody+ T1D with \<10 yr duration
* Age 12-21 years
* BMI ≥ 5%ile
* Weight\<350 lbs and \> 57 lbs.
* No anemia
* HbA1c \<12%

Exclusion Criteria:

* Severe illness, recent diabetic ketoacidosis (DKA)
* Estimated Glomerular Filtration Rate (eGFR) \<60ml/min/1.73m2 or creatinine \> 1.5mg/dl or history of ACR≥300mg/g
* Anemia or allergy to shellfish or iodine
* Pregnancy or nursing
* MRI scanning contraindications (claustrophobia, implantable devices, \>350 lbs)
* Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), diuretics, sodium-glucose co-transport (SGLT) 2 or 1 blockers, daily NSAIDs or aspirin, sulfonamides, procaine, thiazolsulfone or probenecid, atypical antipsychotics and steroids

Primary outcomes:
measure: Copeptin Levels
timeFrame: 4 hours
measure: Effective Renal Plasma Flow (ERPF)
timeFrame: 4 hours
measure: Glomerular Filtration Rate (GFR)
timeFrame: 4 hours
Secondary outcomes:
measure: Renal Perfusion
timeFrame: 10 min
measure: Renal Oxygenation
timeFrame: 60 min
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
Study officials:
affiliation: University of Colorado School of Medicine
name: Petter Bjornstad, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vigers T, Vinovskis C, Li LP, Prasad P, Heerspink H, D'Alessandro A, Reisz JA, Piani F, Cherney DZ, van Raalte DH, Nadeau KJ, Pavkov ME, Nelson RG, Pyle L, Bjornstad P. Plasma levels of carboxylic acids are markers of early kidney dysfunction in young people with type 1 diabetes. Pediatr Nephrol. 2023 Jan;38(1):193-202. doi: 10.1007/s00467-022-05531-3. Epub 2022 May 4.
citation: Vinovskis C, Li LP, Prasad P, Tommerdahl K, Pyle L, Nelson RG, Pavkov ME, van Raalte D, Rewers M, Pragnell M, Mahmud FH, Cherney DZ, Johnson RJ, Nadeau KJ, Bjornstad P. Relative Hypoxia and Early Diabetic Kidney Disease in Type 1 Diabetes. Diabetes. 2020 Dec;69(12):2700-2708. doi: 10.2337/db20-0457. Epub 2020 Jul 31.