Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001184662
Ethics application status
Approved
Date submitted
26/10/2023
Date registered
16/11/2023
Date last updated
2/06/2024
Date data sharing statement initially provided
16/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of exogenous glucose-dependent insulinotropic polypeptide (GIP) on urinary glucose excretion in type 2 diabetes
Scientific title
Effect of exogenous glucose-dependent insulinotropic polypeptide (GIP) on urinary glucose excretion in type 2 diabetes
Secondary ID [1] 310835 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
type 2 diabetes 331844 0
Condition category
Condition code
Metabolic and Endocrine 328589 328589 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following enrolment, each participant will be studied on 2 occasions, separated by at least 7 days, in a double-blinded, randomised, crossover design. On the evening preceding the study day (~1900h), participants will be given a standardised evening meal. Following this meal, participants will be asked to fast from solids and liquids (other than water) until the following morning, when they will attend the Clinical Research Facility (CRF) of the Adelaide Health and Medical Science (AHMS) building at ~0800h.

On each study day, participants will be instructed to defer any morning dose of prescribed medications until the end of the investigation, and an intravenous cannula will be placed into a vein of each forearm for intravenous (IV) dextrose and GIP infusions, and for blood sampling, respectively. A hyperglycaemic clamp will be maintained at 15 mmol/L from t = 0 to 210 min. This will be achieved by intravenous administration of an initial bolus of 25% dextrose (volume calculated to elevate blood glucose to 15 mmol/L from baseline, followed by a 25% dextrose infusion at a rate adjusted according to blood glucose concentrations measured every 5 min using a glucose analyser (Yellow Springs Instrument (YSI) 2500, YSI Life Science Inc, Ohio, USA). Concurrently, an IV infusion of GIP (4 pmol/kg/min; intervention) or 0.9% saline (control) will be administered.

Following an initial 30 min of stabilisation of the hyperglycaemic clamp, participants will be asked to empty their bladder at t = 30 min. Subsequently, participants will consume 250 mL water at t = 30, 60, 90, 120, 150 and 180 min respectively, each within 2 min. Urine samples will be collected every 60 min between t = 30-210 min. The glucose levels in the urine will be measured immediately using a YSI analyser. Urine samples will also be collected for urinary electrolytes (including sodium and potassium). “Arterialised” venous blood will be sampled every 30 min, kept warm with a heat pad, between t = 0 and 210 min for measurement of plasma insulin, C-peptide and glucagon. Serum creatinine will be measured and used for calculating the estimated Glomerular Filtration Rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Renal and superior mesenteric artery blood flow will be measured using ultrasound at baseline, and at t = 120 and 210 min. Blood pressure will be monitored every 15 min from t = 0-210 min.

After a final blood sample is collected, participants will be served a light lunch, and once the blood glucose concentration has stabilised above 5 mmol/L, they will be free to leave the laboratory. The total amount of blood drawn during the screening and 2 study visits will be ~200 mL.
Intervention code [1] 327246 0
Treatment: Drugs
Comparator / control treatment
0.9% saline
Control group
Placebo

Outcomes
Primary outcome [1] 336390 0
The difference in urinary glucose excretion between GIP and placebo days
Timepoint [1] 336390 0
t = 90, 150 and 210 min, where t = 0 is when glucose clamping and GIP/placebo infusion start.
Secondary outcome [1] 428128 0
The difference in urinary electrolyte excretion between GIP and placebo days.
Timepoint [1] 428128 0
t = 90, 150 and 210 min, where t = 0 is when glucose clamping and GIP/placebo infusion start.
Secondary outcome [2] 428129 0
The differences in the amount of glucose required to be infused IV to maintain the hyperglycaemic clamp between GIP and placebo days
Timepoint [2] 428129 0
GIP and placebo study days.
Secondary outcome [3] 428130 0
The differences in estimated renal glucose reabsorption between GIP and placebo days
Timepoint [3] 428130 0
GIP and placebo study days.
Secondary outcome [4] 428131 0
Difference in plasma insulin between GIP and placebo days.
Timepoint [4] 428131 0
t = 30, 60, 90, 120, 150, 180 and 210 min, where t = 0 is when glucose clamping and GIP/placebo infusion start.
Secondary outcome [5] 428132 0
Difference in plasma C-peptide between GIP and placebo days.
Timepoint [5] 428132 0
t = 30, 60, 90, 120, 150, 180 and 210 min, where t = 0 is when glucose clamping and GIP/placebo infusion start.
Secondary outcome [6] 428133 0
Difference in plasma glucagon between GIP and placebo days.
Timepoint [6] 428133 0
t = 30, 60, 90, 120, 150, 180 and 210 min, where t = 0 is when glucose clamping and GIP/placebo infusion start.

Eligibility
Key inclusion criteria
- Type 2 diabetes (American Diabetes Association criteria) treated by diet and/or up to two oral glucose-lowering agents (on stable doses over the last 3 months) except for SGLT2 inhibitors or DPP-4 inhibitors
- Body mass index (BMI) between 20 to 40 kg/m2
- Males and females, aged from 18 to 79 years
- Glycated haemoglobin (HbA1c) between 6.0% to 10.0%
- Haemoglobin above the lower limit of the normal range (ie. above 135 g/L for men and 115 g/L for women), and ferritin above the lower limit of normal (ie. above 30 mg/mL for men and 20 mg/mL for women)
Minimum age
18 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes on a daily basis
- History of any form of heart disease or symptoms of syncope or pre-syncope (including feeling lightheaded or dizzy, feeling unsteady when standing, unexplained falls, fainting, unexplained changes in vision, such as blurring or tunnel vision)
- Other significant illness, including epilepsy, cardiovascular or respiratory disease
- Impaired renal or liver function (as assessed by calculated creatinine clearance less than 60 mL/min or abnormal liver function tests (more than 2 times upper limit of normal range))
- Donation of blood within the previous 3 months
- Participation in any other research studies within the previous 3 months
- Inability to give informed consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/01/2024
Actual
2/02/2024
Date of last participant enrolment
Anticipated
28/02/2025
Actual
Date of last data collection
Anticipated
28/03/2025
Actual
Sample size
Target
20
Accrual to date
7
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 315080 0
University
Name [1] 315080 0
The University of Adelaide
Country [1] 315080 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
Clinical Research Facility, Level 4 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 317101 0
None
Name [1] 317101 0
Address [1] 317101 0
Country [1] 317101 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314028 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 314028 0
Ethics committee country [1] 314028 0
Australia
Date submitted for ethics approval [1] 314028 0
15/06/2023
Approval date [1] 314028 0
26/09/2023
Ethics approval number [1] 314028 0
2023/HRE00157

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130170 0
Prof Chris Ryaner
Address 130170 0
Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 130170 0
Australia
Phone 130170 0
+61 8 8313 6693
Fax 130170 0
Email 130170 0
[email protected]
Contact person for public queries
Name 130171 0
Chris Ryaner
Address 130171 0
Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 130171 0
Australia
Phone 130171 0
+61 8 8313 6693
Fax 130171 0
Email 130171 0
[email protected]
Contact person for scientific queries
Name 130172 0
Chris Ryaner
Address 130172 0
Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 130172 0
Australia
Phone 130172 0
+61 8 8313 6693
Fax 130172 0
Email 130172 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The ethical statement and informed consent do not allow for free data availability.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.