ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12621001106820

Ethics application status

Approved

Date submitted

14/07/2021

Date registered

20/08/2021

Date last updated

14/09/2023

Date data sharing statement initially provided

20/08/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

Optimum Diagnostic Testing for Glucocorticoid Induced Hyperglycaemia

Scientific title

Optimum Diagnostic Testing for Glucocorticoid Induced Hyperglycaemia

Secondary ID [1]

nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Diabetes induced by Glucocorticoids

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

This trial will evaluate the optimum diagnostic testing for prednisolone induced hyperglycaemia. Participants who are taking prednisolone for greater than 3 months at a dose of greater than 4 mg, will be asked to participate in this study.

Participants who have consented to take part in the study, who are taking greater than 4 mg of prednisolone will each undergo an oral glucose tolerance test (OGTT) and a random afternoon blood glucose on a separate day and at least 48 hours after their OGTT

Exposure 1, Oral glucose tolerance test (OGTT) - The participant will be fasting from 10 pm prior to the day of their OGTT. They will then present to our Endocrine clinic the following morning. (Marion GP plus, Adelaide South Australia) On arrival in the morning, they will be met by one of the study investigators and have their BMI calculated, waist and hip circumference measured, and an intravenous cannula will be inserted by one the study investigators. Each investigator that has participant contact will be either a medical doctor with greater than 5 years experience, or a study nurse with more than 5 years experience. A blood sample will be taken from this cannula on insertion. The following markers will be tested for as a baseline
1) Glycosylated Haemoglobin
2) Fasting Glucose
3) Liver Function Tests
4) Lipid Profile
5) C-reactive protein
6) Renal function
7) Fasting insulin concentration

Participants will then be given an oral glucose load of 75 grams which they will consume orally. They will remain on site at the clinic for 2 hours, after which a second blood sample will be taken to monitor their blood glucose levels. Participants will then have their Intravenous cannula removed and this will complete the first intervention. The total anticipated duration of the OGTT session will take up to 2.5 hours.

Exposure 2, Random afternoon glucose – Each participant on a separate day and at least 48 hours after their OGGT, will undergo a blood test at a pathology collection (SA Pathology) centre to measure a random afternoon blood glucose. This test will take place between 2 pm and 6 pm. The total duration of this session will be no more than 15 minutes

Each participants fasting glucose, oral glucose tolerance test and random afternoon blood glucose results will be reviewed to determine the difference in diagnostic accuracy between these modalities

Intervention code [1]

Diagnosis / Prognosis

Comparator / control treatment

no control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

The primary endpoint is the difference in sensitivity between fasting glucose and random afternoon glucose to diagnose diabetes, as estimated by the area under their respective receiver operator characteristic curves. The diagnosis of diabetes will be defined by the current gold-standard, an oral glucose tolerance test.

Timepoint [1]

Baseline

Secondary outcome [1]

No prespecified secondary outcomes

Timepoint [1]

No prespecified secondary outcomes

Eligibility

Key inclusion criteria

1) Age greater than or equal to 18 years.
2) Prescribed greater than 4 mg of prednisolone per day for at least 3 months

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1) Known diabetes
2) Transaminase LFT derangement (greater than 3 times the upper limit of normal)
3) Acute or chronic pancreatitis
4) Glycogen storage diseases
5) Pregnancy
6) Creatinine clearance less than 30 ml/min

Study design

Purpose

Screening

Duration

Cross-sectional

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

We will evaluate the receiver operating characteristic curve and area under the curve for the different diagnostic tests.

We note previous studies that have estimated the prevalence of undiagnosed diabetes is 15% in this participants taking >4 mg of prednisolone. A sample of 15 positive and 85 negative cases has 80% power to detect a difference of 0.2 between a diagnostic test with an area under the ROC curve (AUC) of 0.7 and another diagnostic test with an AUC of 0.9 using a two sided Z-test, at a significance level of 0.05. The correlation between the two diagnostic tests is assumed to be 0.6 in our calculations.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

6/09/2021

Actual

10/09/2021

Date of last participant enrolment

Anticipated

1/02/2024

Actual

Date of last data collection

Anticipated

8/02/2024

Actual

Sample size

Target

100

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Flinders Medical Centre - Bedford Park

Recruitment hospital [2]

Noarlunga Health Service - Noarlunga Centre

Recruitment hospital [3]

Repatriation General Hospital - Daw Park

Recruitment postcode(s) [1]

5042 - Bedford Park

Recruitment postcode(s) [2]

5168 - Noarlunga Centre

Recruitment postcode(s) [3]

5041 - Daw Park

Funding & Sponsors

Funding source category [1]

University

Name [1]

Flinders University

Address [1]

Sturt Road, Bedford Park SA 5042

Country [1]

Australia

Primary sponsor type

Individual

Name

Associate Professor Morton Burt

Address

Southern Adelaide Diabetes and Endocrine Services (SADES)
GP Plus Marion
10 Milham St, Oaklands Park SA 5046

Country

Australia

Secondary sponsor category [1]

Hospital

Name [1]

Flinders Medical Centre

Address [1]

Flinders Drive, Bedford Park SA 5042

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Adelaide Clinical Human Research Ethics Committee

Ethics committee address [1]

Flinders Drive, Bedford Park SA 5042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

21/06/2021

Approval date [1]

26/07/2021

Ethics approval number [1]

2021/HRE00191

Summary

Brief summary

We hypothesise that a random afternoon glucose has superior sensitivity to a fasting blood glucose to diagnose diabetes in patients taking long-term prednisolone.
Hyperglycaemia is a known adverse effect of Prednisolone and previous research has demonstrated that the pattern of hyperglycaemia seen in patients taking prednisolone, typically occurs in the afternoon with less of an effect on morning fasting blood glucose levels. 
In the clinical setting, the diagnosis of diabetes can made via different testing modalities. Taking into account the pattern of hyperglycaemia caused by prednisolone, the sensitivity of each of the diagnostic modalities may vary. As a result, we will compare a random afternoon blood glucose to a morning fasting glucose. These two testing modalities will be compared to the current gold standard test which is an oral glucose tolerance test.

Trial website

Trial related presentations / publications

Public notes

Introduction
Prednisolone is a commonly used, oral semi-synthetic glucocorticoid hormone that can cause insulin resistance and diabetes. Currently, the best way to diagnose Prednisolone-associated diabetes and insulin resistance is not well defined. Our Unit previously reported that an oral glucose tolerance test was a superior test to diagnose diabetes than measuring fasting glucose or glycosylated haemoglobin (HbA1c) in this patient group. However, an oral glucose tolerance test is more time consuming for patients and costs more than single glucose measurements. We have also reported that glucose is typically highest in the late afternoon in hospitalised patients prescribed Prednisolone. We hypothesise that an afternoon random blood glucose will have superior sensitivity and specificity to diagnose Prednisolone-associated diabetes than fasting blood glucose

Background
In patients with inflammatory disease, low to moderate doses of prednisolone are commonly incorporated into pharmacological regimes for initial disease control, or as a bridge to disease modifying or biological treatment. The prevalence of long-term oral glucocorticoid use in the community is 0.75-1.2%.
Prednisolone, even at low doses, causes insulin resistance and can increase blood glucose and cause diabetes. Studies have reported that the prevalence of undiagnosed diabetes in patients taking prednisolone was 15% and that an OGTT has a greater sensitivity to diagnose diabetes. However, prednisolone mainly increases glucose levels in the afternoon and early evening. Therefore, it was proposed that an afternoon random glucose should be used to screen for diabetes in patients taking prednisolone. If effective, this would represent a convenient and cost-effective test to diagnose diabetes in this patient group. However, there are no studies investigating the efficacy of this approach.

Rationale/Justification
Investigating accurate diagnostic screening for diabetes in this population may lead to earlier diagnosis and potentially more convenient and cost effective testing for patients taking prednisolone 

Hypothesis
A random afternoon glucose is superior to a fasting blood glucose to diagnose diabetes in patients taking long-term prednisolone.

Aim
To investigate if a random afternoon blood glucose is a superior to fasting blood glucose in the diagnosis of prednisolone induced hyperglycaemia.

Objectives
Participants meeting inclusion and exclusion criteria will be recruited to undergo an oral glucose tolerance test (which is the gold-standard test for diabetes and includes a fasting glucose measurement) and measurement of a random afternoon glucose. We will analyse whether the afternoon glucose concentration is a superior test for diabetes compared to a fasting glucose in this patient group. The oral glucose tolerance test will determine the overall prevalence of diabetes.

Contacts

Principal investigator

Name

A/Prof Morton Burt

Address

Southern Adelaide Diabetes and Endocrine Services (SADES)
Marion GP Plus Health Care Centre, Level 2, 10 Milham Street, Oaklands Park, South Australia 5046

Country

Australia

Phone

+61 8 7425 8690

Fax

+61 8 7425 8689

morton.burt@sa.gov.au

Contact person for public queries

Name

Morton Burt

Address

Southern Adelaide Diabetes and Endocrine Services (SADES)
Marion GP Plus Health Care Centre, Level 2, 10 Milham Street, Oaklands Park, South Australia 5046

Country

Australia

Phone

+61 8 7425 8690

Fax

+61 8 7425 8689

morton.burt@sa.gov.au

Contact person for scientific queries

Name

Morton Burt

Address

Southern Adelaide Diabetes and Endocrine Services (SADES)
Marion GP Plus Health Care Centre, Level 2, 10 Milham Street, Oaklands Park, South Australia 5046

Country

Australia

Phone

+61 8 7425 8690

Fax

+61 8 7425 8689

morton.burt@sa.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

The data that will be shared will be de-identified
The following data will be shared
Glycosylated Haemoglobin
Fasting Glucose
Glucose level post 75 gram Glucose load
Random Afternoon Blood Glucose level (between 2pm and 6pm)
C-reactive protein
Waist and hip circumference
Body Mass Index

When will data be available (start and end dates)?

Start date - Immediately following publication
End Date - No end date determined

Available to whom?

Anyone who wishes to access it

Available for what types of analyses?

No specific type of analysis

How or where can data be obtained?

Once the study has been published, the results will be available online from https://pubmed.ncbi.nlm.nih.gov/ or the publisher's web address
For any data not published (such as baseline renal and liver function), then access will be subject to approval by the principal investigator - A/Prof Morton Burt
Email - morton.burt@sa.gov.au

What supporting documents are/will be available?

Doc. No.	Type	Email	Other Details	Attachment
12537	Study protocol	faran.khalili@sa.gov.au		382312-(Uploaded-01-08-2021-13-02-32)-Study-related document.docx
12538	Informed consent form	faran.khalili@sa.gov.au		382312-(Uploaded-14-07-2021-14-20-19)-Study-related document.docx
12539	Ethical approval		Ethics has now been approved and I have attached t... [More Details]	382312-(Uploaded-18-08-2021-12-29-25)-Study-related document.docx
12931	Other		This is the site specific agreement and governance... [More Details]	382312-(Uploaded-18-08-2021-12-29-25)-Study-related document.pdf

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