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Copeptin in Adolescent Participants With Type 1 Diabetes and Early Renal Hemodynamic Function (CASPER)

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ClinicalTrials.gov Identifier: NCT03618420
Recruitment Status : Completed
First Posted : August 7, 2018
Results First Posted : August 31, 2021
Last Update Posted : April 20, 2022
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Diagnostic
Conditions Diabetes Mellitus, Type 1
Nephropathy
Diabetic Nephropathies
Juvenile Diabetes
Diabetes Mellitus Complication
Autoimmune Diabetes
Type 1 Diabetes Mellitus
Interventions Drug: Aminohippurate Sodium Inj 20%
Drug: Iohexol Inj 300 mg/mL
Enrollment 50
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Clinical Investigation
Hide Arm/Group Description

All participants will undergo assessment of Glomerular Filtration Rate, (Iohexol Inj 300 mg/mL) and Effective Renal Plasma Flow (Aminohippurate Sodium Inj 20%). In addition, participants will undergo imaging assessment that includes Dual X-Ray Absorptiometry (DXA), renal Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labeling (ASL) MRI.

Aminohippurate Sodium Inj 20%: Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Iohexol Inj 300 mg/mL: Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Period Title: Overall Study
Started [1] 50
Completed 50
Not Completed 0
[1]
Study Start and IRB Approval
Arm/Group Title Clinical Investigation
Hide Arm/Group Description

All participants will undergo assessment of Glomerular Filtration Rate, (Iohexol Inj 300 mg/mL) and Effective Renal Plasma Flow (Aminohippurate Sodium Inj 20%). In addition, participants will undergo imaging assessment that includes Dual X-Ray Absorptiometry (DXA), renal Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labeling (ASL) MRI.

Aminohippurate Sodium Inj 20%: Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Iohexol Inj 300 mg/mL: Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Overall Number of Baseline Participants 50
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 50 participants
16.0  (3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Female
25
  50.0%
Male
25
  50.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Black non-Hispanic
1
   2.0%
Hispanic
3
   6.0%
White non-Hispanic
46
  92.0%
1.Primary Outcome
Title Copeptin Levels
Hide Description Measured by fasting blood draw; Copeptin will be measured by ultrasensitive assays on KRYPTOR Compact Plus analyzers using the commercial sandwich immunoluminometric assays (Thermo Fisher Scientific, Waltham, MA). The copeptin assay has a lower limit of detection of 0.9 pmol/L, and a sensitivity of <2pmol/L. Elevated copeptin will be defined as >13pmol/L, which is >97.5th percentile for healthy adults (68).
Time Frame 4 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The overall number of participants analyzed for the outcome measure Copeptin levels is 49 because of an assay issue, specifically one of the samples failed during quality control.
Arm/Group Title Clinical Investigation
Hide Arm/Group Description:

All participants will undergo assessment of Glomerular Filtration Rate, (Iohexol Inj 300 mg/mL) and Effective Renal Plasma Flow (Aminohippurate Sodium Inj 20%). In addition, participants will undergo imaging assessment that includes Dual X-Ray Absorptiometry (DXA), renal Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labeling (ASL) MRI.

Aminohippurate Sodium Inj 20%: Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Iohexol Inj 300 mg/mL: Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Overall Number of Participants Analyzed 49
Mean (Standard Deviation)
Unit of Measure: pmol/L
8.3  (5.0)
2.Primary Outcome
Title Effective Renal Plasma Flow (ERPF)
Hide Description Measured by para-aminohippurate (PAH) clearance; An intravenous (IV) line was placed, and participants were asked to empty their bladders. Spot plasma and urine samples were collected prior PAH infusion. PAH (2 g/10 mL, prepared at the University of Minnesota, with a dose of [weight in kg]/75 × 4.2 mL; IND #140129) was given slowly over 5 min followed by a continuous infusion of 8 mL of PAH and 42 mL of normal saline at a rate of 24 mL/h for 2 h. After an equilibration period, blood was drawn at 90 and 120 min, and ERPF was calculated as PAH clearance divided by the estimated extraction ratio of PAH, which varies by the level of GFR (13). We report absolute ERPF (mL/min) in the main analyses because the practice of indexing ERPF for body surface underestimates hyperperfusion, and body surface area (BSA) calculations introduce noise into the clearance measurements.
Time Frame 4 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The overall number of participants analyzed for the outcome measure ERPF is 37 because PAH was unavailable for several of the first study visits.
Arm/Group Title Clinical Investigation
Hide Arm/Group Description:

All participants will undergo assessment of Glomerular Filtration Rate, (Iohexol Inj 300 mg/mL) and Effective Renal Plasma Flow (Aminohippurate Sodium Inj 20%). In addition, participants will undergo imaging assessment that includes Dual X-Ray Absorptiometry (DXA), renal Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labeling (ASL) MRI.

Aminohippurate Sodium Inj 20%: Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Iohexol Inj 300 mg/mL: Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: ml/min
820  (125)
3.Primary Outcome
Title Glomerular Filtration Rate (GFR)
Hide Description Measured by iohexol clearance; An intravenous (IV) line was placed, and participants were asked to empty their bladders. Spot plasma and urine samples were collected prior to iohexol infusion. Iohexol was administered through bolus IV injection (5 mL of 300 mg/mL; Omnipaque 300, GE Healthcare). An equilibration period of 120 min was used and blood collections for iohexol plasma disappearance were drawn at +120, +150, +180, +210, +240 min (11). Because the Brøchner-Mortensen equation underestimates high values of GFR, the Jødal-Brøchner-Mortensen equation was used to calculate the GFR (12). We report absolute GFR (mL/min) in the main analyses because the practice of indexing GFR for body surface underestimates hyperfiltration, and body surface area (BSA) calculations introduce noise into the clearance measurements.
Time Frame 4 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Clinical Investigation
Hide Arm/Group Description:

All participants will undergo assessment of Glomerular Filtration Rate, (Iohexol Inj 300 mg/mL) and Effective Renal Plasma Flow (Aminohippurate Sodium Inj 20%). In addition, participants will undergo imaging assessment that includes Dual X-Ray Absorptiometry (DXA), renal Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labeling (ASL) MRI.

Aminohippurate Sodium Inj 20%: Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Iohexol Inj 300 mg/mL: Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: ml/min
189  (40)
4.Secondary Outcome
Title Renal Perfusion
Hide Description Measured by Arterial Spin Labeling (ASL) MRI; ASL MRI: ROI analysis will be used to estimate (delta) M (difference in signal intensity between non-selective and selective inversion images). Using the same ROI, M0 will be estimated from the proton density image. T1 measurements from the same ROI will be obtained by fitting the signal intensity vs. inversion time data as described previously (104) using XLFit (ID Business Solutions Ltd., UK) or T1 maps created using MRI Mapper (Beth Israel Deaconess Medical Center, Boston). Partition coefficient will be assumed to be 0.8 ml/gm (105, 106). These values will then be used to estimate regional blood flow.
Time Frame 10 min
Hide Outcome Measure Data
Hide Analysis Population Description
The overall number of participants analyzed for the outcome measure Renal Perfusion is 45 because scans did not meet the high quality control standard of our MRI reader and thus were omitted.
Arm/Group Title Clinical Investigation
Hide Arm/Group Description:

All participants will undergo assessment of Glomerular Filtration Rate, (Iohexol Inj 300 mg/mL) and Effective Renal Plasma Flow (Aminohippurate Sodium Inj 20%). In addition, participants will undergo imaging assessment that includes Dual X-Ray Absorptiometry (DXA), renal Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labeling (ASL) MRI.

Aminohippurate Sodium Inj 20%: Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Iohexol Inj 300 mg/mL: Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Overall Number of Participants Analyzed 45
Mean (Standard Deviation)
Unit of Measure: ml/min/100g
180  (39)
5.Secondary Outcome
Title Renal Oxygenation
Hide Description Measured by Blood Oxygen Level Dependent (BOLD) MRI; Regions of interest (ROI) analysis for BOLD MRI will be performed on a Leonardo Workstation (Siemens Medical Systems, Germany). Typically, 1 to 3 regions in each, cortex and medulla, per kidney per slice will be defined leading to a total of about 10 ROIs per region (cortex and medulla) per subject. The mean and standard deviation of these 10 measurements will be used a R2* measurement for the region, for the subject and for that time point. These data are used to calculate kidney oxygen availability (R2*), which is the BOLD-MRI outcome.
Time Frame 60 min
Hide Outcome Measure Data
Hide Analysis Population Description
The overall number of participants analyzed for the outcome measure Renal Oxygenation is 41 because scans did not meet the high quality control standard of our MRI reader and thus were omitted.
Arm/Group Title Clinical Investigation
Hide Arm/Group Description:

All participants will undergo assessment of Glomerular Filtration Rate, (Iohexol Inj 300 mg/mL) and Effective Renal Plasma Flow (Aminohippurate Sodium Inj 20%). In addition, participants will undergo imaging assessment that includes Dual X-Ray Absorptiometry (DXA), renal Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labeling (ASL) MRI.

Aminohippurate Sodium Inj 20%: Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Iohexol Inj 300 mg/mL: Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Overall Number of Participants Analyzed 41
Mean (Standard Deviation)
Unit of Measure: s^-1
22.7  (2.2)
Time Frame Adverse events were collected over 1 month post procedure (since this was a cross-sectional study).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Clinical Investigation
Hide Arm/Group Description

All participants will undergo assessment of Glomerular Filtration Rate, (Iohexol Inj 300 mg/mL) and Effective Renal Plasma Flow (Aminohippurate Sodium Inj 20%). In addition, participants will undergo imaging assessment that includes Dual X-Ray Absorptiometry (DXA), renal Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labeling (ASL) MRI.

Aminohippurate Sodium Inj 20%: Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Iohexol Inj 300 mg/mL: Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

All-Cause Mortality
Clinical Investigation
Affected / at Risk (%)
Total   0/50 (0.00%) 
Hide Serious Adverse Events
Clinical Investigation
Affected / at Risk (%)
Total   0/50 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Clinical Investigation
Affected / at Risk (%)
Total   2/50 (4.00%) 
Nervous system disorders   
Headache/lightheadedness/nausea * [1]  1/50 (2.00%) 
Vascular disorders   
Vasovagal syncope * [2]  1/50 (2.00%) 
*
Indicates events were collected by non-systematic assessment
[1]
Participant experienced headache and lightheadedness during screening visit when blood draw to obtain screening labs was attempted. This is a known risk which is included in the consent form.
[2]
Participant experienced vasovagal syncope as a result of anxiety and peripheral intravenous line (PIV) placement at the beginning of study visit; known risk which is included in the consent form.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Petter Bjornstad, M.D., Assistant Professor of Pediatrics and Medicine
Organization: University of Colorado School of Medicine
Phone: 7207774659
EMail: petter.bjornstad@childrenscolorado.org
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03618420    
Other Study ID Numbers: 17-0820
First Submitted: August 1, 2018
First Posted: August 7, 2018
Results First Submitted: August 5, 2021
Results First Posted: August 31, 2021
Last Update Posted: April 20, 2022