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Trial registered on ANZCTR


Registration number
ACTRN12623000094673
Ethics application status
Approved
Date submitted
19/01/2023
Date registered
27/01/2023
Date last updated
26/06/2024
Date data sharing statement initially provided
27/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Acute effect of the renally excreted low-calorie sweetener, acesulfame potassium (Ace-K), on urinary glucose excretion in people with type 2 diabetes.
Scientific title
Acute effect of the renally excreted low-calorie sweetener, acesulfame potassium (Ace-K), on urinary glucose excretion in people with type 2 diabetes.
Secondary ID [1] 308791 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 328740 0
Condition category
Condition code
Metabolic and Endocrine 325746 325746 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following enrolment, each participant will be studied on 3 occasions, separated by at least 3 days, in a double-blinded, randomised, crossover design. On the evening preceding the study day (~1900h), participants will be given a standardised evening meal (McCain beef Lasagne 400g, 592 kcal with 66% carbohydrate, 17% protein and 17% fat). 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 CRF of the 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 IV dextrose infusion and 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 as previously described), followed by a 25% dextrose infusion at a rate adjusted according to blood glucose concentrations measured every 5 min using a YSI analyser. 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 400 mL water together with a gelatin capsule containing (i) 175 mg Ace-K, (ii) 58 mg sucralose (of equal sweetness to the dose of Ace-K) + 117 mg cellulose or (iii) 175 mg cellulose (placebo) at t = 30, 60, 90, 120, 150 and 180 min respectively, each within 5 min (the doses of Ace-K and sucralose are calculated based on ADI at 70 kg of body weight). 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. “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. Serum creatinine will be measured and used for calculating eGFR by the CKD-EPI formula. Renal artery blood flow will be measured using ultrasound at t = 30 and 210 min.

After a final blood sample is collected, participants will be served a light lunch (a sandwich ordered from a Cafe within the building, approximately 350 kcal with 60% carbohydrate, 20% protein and 20% fat; a yoghurt, ~140 kcal with 60% carbohydrate, 30% protein and 10% fat) with water and once the blood concentration has stabilised above 5 mmol/L, they will be free to leave the laboratory.
Intervention code [1] 325244 0
Treatment: Other
Comparator / control treatment
Placebo capsule (cellulose)
Control group
Placebo

Outcomes
Primary outcome [1] 333595 0
The difference in accumulated urinary glucose excretion (= urine glucose concentrations * urine volume) between Ace-K, sucralose and placebo days.
Timepoint [1] 333595 0
t = 30, 90, 150 and 210 min, where t = 0 is when glucose clamping starts and t = 30 is when first dose of Ace-k/sucralose/placebo is given, on three study days.
Secondary outcome [1] 417688 0
The difference in estimated renal glucose reabsorption (plasma glucose levels * glomerular filtration rate * 180min - accumulated urinary glucose excretion from t = 30 to 210min) between Ace-K, sucralose and placebo days.
Timepoint [1] 417688 0
t = 30, 90, 150 and 210 min, where t = 0 is when glucose clamping starts and t = 30 is when the first dose of Ace-k/sucralose/placebo is given, on three study days.
Secondary outcome [2] 417689 0
The difference in the amount of glucose infused intravenously (quantified by the infusion pump) to maintain the hyperglycaemic clamp between Ace-K, sucralose and placebo days.
Timepoint [2] 417689 0
Placebo visit, Ace-K visit and sucralose visit
Secondary outcome [3] 417690 0
The difference in plasma insulin levels between Ace-K, sucralose and placebo days.
Timepoint [3] 417690 0
where t = 0 is when glucose clamping starts and t = 30 is when the first dose of Ace-k/sucralose/placebo is given, on three study days.

Eligibility
Key inclusion criteria
- Type 2 diabetes (American Diabetes Association criteria) treated by diet and/or one or two oral glucose-lowering agents (on stable doses over the last 3 months) except for SGLT2 inhibitors
- Body mass index (BMI) from 20 to 40 kg/m2, and body weight over 70 kg
- Males and females, aged from 40 to 79 years
- Glycated haemoglobin (HbA1c) above 6.0%, but less than 7.9%
- Haemoglobin above the lower limit of the normal range (ie. above 135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. above 30ng/mL for men and above 20mg/mL for women)
Minimum age
40 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Habitual use of more than one serve of any food or beverage containing a LCS per day during the past 3 months, ascertained using a LCS frequency questionnaire.
- 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
- Vegetarians

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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on our recent observations on the effect of an acute dose of Ace-K on urinary glucose excretion after a 50g oral glucose drink in healthy humans, we anticipate that 14 T2D participants will provide at least 80% power to detect ~30% difference in the excretion of urinary glucose over 3 hours. 16 participants will be recruited to allow for drop-outs.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/02/2023
Actual
1/03/2023
Date of last participant enrolment
Anticipated
1/03/2024
Actual
20/11/2023
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
16
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 313007 0
Charities/Societies/Foundations
Name [1] 313007 0
The Hospital Research Foundation
Country [1] 313007 0
Australia
Funding source category [2] 313010 0
Charities/Societies/Foundations
Name [2] 313010 0
The Hospital Research Foundation
Country [2] 313010 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] 314697 0
None
Name [1] 314697 0
None
Address [1] 314697 0
None
Country [1] 314697 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312271 0
Central Adelaide Local Health Network HREC Human Research Ethics Committee
Ethics committee address [1] 312271 0
Ethics committee country [1] 312271 0
Australia
Date submitted for ethics approval [1] 312271 0
20/11/2022
Approval date [1] 312271 0
19/12/2022
Ethics approval number [1] 312271 0
2022/HRE00300

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

Contacts
Principal investigator
Name 124058 0
A/Prof Tongzhi Wu
Address 124058 0
Adelaide Medical School, the University of Adelaide
Level 6 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace,
Adelaide, SA 5000
Country 124058 0
Australia
Phone 124058 0
+61 8 8313 6535
Fax 124058 0
Email 124058 0
[email protected]
Contact person for public queries
Name 124059 0
Tongzhi Wu
Address 124059 0
Adelaide Medical School, the University of Adelaide
Level 6 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace,
Adelaide, SA 5000
Country 124059 0
Australia
Phone 124059 0
+61 8 8313 6535
Fax 124059 0
Email 124059 0
[email protected]
Contact person for scientific queries
Name 124060 0
Tongzhi Wu
Address 124060 0
Adelaide Medical School, the University of Adelaide
Level 6 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace,
Adelaide, SA 5000
Country 124060 0
Australia
Phone 124060 0
+61 8 8313 6535
Fax 124060 0
Email 124060 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

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