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Trial registered on ANZCTR


Registration number
ACTRN12612001302842
Ethics application status
Approved
Date submitted
7/12/2012
Date registered
17/12/2012
Date last updated
17/12/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Pathogenic Mechanisms Associated with Abnormalities in Post Transplant Glucose Metabolism
Scientific title
Pathogenic Mechanisms Associated with Abnormalities in Post Transplant Glucose Metabolism
Secondary ID [1] 281632 0
Nil
Universal Trial Number (UTN)
U1111-1137-7344
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post transplant diabetes 287918 0
Condition category
Condition code
Metabolic and Endocrine 288295 288295 0 0
Diabetes
Renal and Urogenital 288296 288296 0 0
Kidney disease

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
1. The full 13 time-point Area Under Curve 0-12 (fAUC) for free and total prednisolone will be calculated for each pharmacokinetic profile using the linear trapezoidal rule. Using 15 previously derived limited sampling strategies, predicted AUCs (pAUC) for free prednisolone will be calculated using the appropriate time-points required.
2. After completion of experiment 1, the relationship between blood glucose, free prednisolone exposure and two alternative oral prednisolone dosing strategies will be investigated using continuous glucose monitoring (CGM) in a crossover study of subjects 3-4 weeks post­transplant. Subjects will be randomized from the time of transplantation to daily (QD) (8:00hrs) or divided twice daily (BD) (8:00hrs and 20:00hrs) prednisolone dosing regimens. The prednisolone doses will then adjusted according to the patient’s transplant physician until week three when the total daily prednisolone dose will be fixed for the 5-day study period. Subjects will remain on their randomized dosing regimen for days 1 and 2 before crossover on day 3 to the alternate dosing regimen, i.e. BD to QD, or QD to BD. Day 3 results will be disregarded as a washout period. The iPro2 (registered trade mark) CGM system will be placed on day 1 prior to the morning prednisolone dose at 8:00hrs and removed after 8:00hrs on day 6. Therefore two days of CGM on each dosing regimen will be available for comparison (days 1-2 versus days 4-5). Two Medtronic iPro2 (registered trade mark) CGM systems will be used with Medtronic Enlite (registered trade mark) glucose sensors (Medtronic, California, USA). This system records an average blood sugar measurement every 5 minutes, for up to 6 days at a time. The results are blinded-to-patient and were downloaded using Medtronic CareLink (registered trade mark) iPro (registered trade mark) software. The CGM will be calibrated using the Abbott Optium Xceed (registered trade mark) blood glucose monitoring system with four fingerstick capillary glucose tests per day occurring prior to meals and at bedtime (Abbott Laboratories, Illinois, USA). The study period of 3 to 4 weeks post transplant was chosen as subjects will generally have stabilised after transplant surgery and will remain on moderately high prednisolone doses at that time.
3. Simultaneous with experiment 1 and 2, we will compare the sensitivity and specificity of available diagnostic investigations for post transplant diabetes mellitus (PTDM) at 6 weeks, 12 weeks and 12 months post­transplant fasting plasma glucose (FPG) greater than or equal to 7mmol/L, 2h­post oral glucose tolerance test greater than or equal to 11.1mmol/L, glycated haemoglobin (HbA1c) greater than or equal to 6.5%; pre­dinner home glucometer testing greater than or equal to 11.1mmol/L).
Intervention code [1] 286167 0
Not applicable
Comparator / control treatment
No treatment
Control group
Active

Outcomes
Primary outcome [1] 288471 0
1. Correlation between full measured AUC and predicted AUC using limited sampling strategies
Timepoint [1] 288471 0
1. Assessment will be conducted on one day between 3-4 weeks post-transplant
Primary outcome [2] 288472 0
2. Using a limited sampling strategy for predicting free prednisolone exposure and continuous glucose monitoring we will determine the difference in free prednisolone levels and peak glucose (time and level) between daily and twice daily divided dose prednisolone administration
Timepoint [2] 288472 0
2. Assessment will be conducted over 5 days between 3-4 weeks post-transplant
Primary outcome [3] 288473 0
3. Compare three alternative PTDM diagnostic methods (FPG greater than or equal to 7mmol/L, HbA1c greater than or equal to 6.5%; afternoon home glucometer testing greater than or equal to 11.1mmol/L) with the ‘gold standard’ (75g OGTT).
Timepoint [3] 288473 0
Alternative diagnostic methods will be tested at 6 weeks, 12 weeks and 12 months post-transplant
Secondary outcome [1] 300255 0
1.Relationship between free and total prednisolone AUC and glucose
Timepoint [1] 300255 0
1. Assessment will be conducted on one day between 3-4 weeks post-transplant
Secondary outcome [2] 300256 0
2. 48 hour mean glucose, minimum glucose and area under the glucose curve (calculated by the trapezoid rule) will be assessed from CGM data.
Timepoint [2] 300256 0
2. Assessment will be conducted over 5 days between 3-4 weeks post-transplant
Secondary outcome [3] 300257 0
The prevalence of hyperglycemia during the initial admission after transplantation will be assessed using routine inpatient capillary blood glucose testing results.
Timepoint [3] 300257 0
The initial post-transplantation admission

Eligibility
Key inclusion criteria
Patients who received a kidney transplant at the Royal Melbourne Hospital between February 2008 and October 2012.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A prior diagnosis of diabetes and current or planned pregnancy.

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/07/2010
Actual
8/02/2011
Date of last participant enrolment
Anticipated
31/10/2012
Actual
25/10/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
310
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 305 0
Royal Melbourne Hospital - City campus - Parkville

Funding & Sponsors
Funding source category [1] 286440 0
Hospital
Name [1] 286440 0
Royal Melbourne Hospital Home Lottery Grant in Aid
Country [1] 286440 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital Home Lottery Grant in Aid
Address
Grattan St
Parkville
Victoria 3050
Country
Australia
Secondary sponsor category [1] 285226 0
Commercial sector/Industry
Name [1] 285226 0
Novo Nordisk Regional Diabetes Support Scheme Grant in Aid
Address [1] 285226 0
Novo Nordisk Australia
Level 3
21 Solent Circuit
BAULKHAM HILLS NSW 2153
AUSTRALIA
Country [1] 285226 0
Australia
Secondary sponsor category [2] 285227 0
Charities/Societies/Foundations
Name [2] 285227 0
Australian and New Zealand Society of Nephrology-AMGEN Research Grant
Address [2] 285227 0
145 Macquarie Street
Sydney NSW 2000
Australia
Country [2] 285227 0
Australia
Other collaborator category [1] 277214 0
None
Name [1] 277214 0
Nil
Address [1] 277214 0
Nil
Country [1] 277214 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288517 0
Melbourne Health HREC
Ethics committee address [1] 288517 0
Royal Melbourne Hospital
Grattan St
Parkville
Victoria 3050
Ethics committee country [1] 288517 0
Australia
Date submitted for ethics approval [1] 288517 0
28/05/2010
Approval date [1] 288517 0
26/07/2010
Ethics approval number [1] 288517 0
2010.122

Summary
Brief summary
We aim to:
1. Determine a practical method for measuring exposure to prednisolone and whether exposure to prednisolone correlates with blood glucose.
2. Determine if divided daily prednisolone dosing strategies reduce free prednisolone and glucose levels compared with daily dosing in post-kidney transplant recipients.
3. Determine if afternoon home blood glucose and HbA1c are superior to FPG and OGTT for diagnosing post transplant diabetes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36454 0
Dr Christopher J Yates
Address 36454 0
Dept Diabetes and Endocrinology
Royal Melbourne Hospital
Grattan St
Parkville
Victoria 3050
Country 36454 0
Australia
Phone 36454 0
+61 3 93427000
Fax 36454 0
Email 36454 0
[email protected]
Contact person for public queries
Name 36455 0
Christopher J Yates
Address 36455 0
Dept Diabetes and Endocrinology
Royal Melbourne Hospital
Grattan St
Parkville
Victoria 3050
Country 36455 0
Australia
Phone 36455 0
+61 3 93427000
Fax 36455 0
Email 36455 0
[email protected]
Contact person for scientific queries
Name 36456 0
Christopher J Yates
Address 36456 0
Dept Diabetes and Endocrinology
Royal Melbourne Hospital
Grattan St
Parkville
Victoria 3050
Country 36456 0
Australia
Phone 36456 0
+61 3 93427000
Fax 36456 0
Email 36456 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



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