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Trial registered on ANZCTR


Registration number
ACTRN12624000800527
Ethics application status
Approved
Date submitted
21/06/2024
Date registered
28/06/2024
Date last updated
28/06/2024
Date data sharing statement initially provided
28/06/2024
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 healthy humans.
Scientific title
Acute effect of the renally excreted low-calorie sweetener, acesulfame potassium (Ace-K), on urinary glucose excretion in healthy humans.
Secondary ID [1] 312386 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 334189 0
Condition category
Condition code
Metabolic and Endocrine 330848 330848 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following enrolment, healthy participants will be studied on 2 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, 2529 kJ 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 Clinical Research Facility of the Adelaide Health and Medical Science building at ~0800h.

On each study day, 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 10 mmol/L from t = 0 to 210 min, by intravenous administration of 25% dextrose. 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 together with 5 gelatin capsules containing a total dose of (i) 900 mg Ace-K (calculated based on acceptable daily intake at 60 kg of body weight), or (ii) 900 mg cellulose (placebo) at t = 30 min and 250 mL water every 30 min between t = 60 to 180 min respectively, each within 5 min.

In both groups, 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 Yellow Springs Instruments (YSI) 2900 analyser. “Arterialised” venous blood will be sampled every 30 min, kept warm with a heating pad, between t = 0 and 210 min for measurement of plasma insulin. Serum creatinine will be measured and used for calculating the estimated Glomerular Filtration Rate (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 4 mmol/L for 30 min, they will be free to leave the laboratory.
Intervention code [1] 328886 0
Treatment: Other
Comparator / control treatment
Placebo capsule (cellulose)
Control group
Placebo

Outcomes
Primary outcome [1] 338618 0
The difference in accumulated urinary glucose excretion (= urine glucose concentrations * urine volume) between Ace-K and placebo days in healthy participants.
Timepoint [1] 338618 0
t = 30, 90, 150 and 210 min, where t = 0 is when glucose clamping starts and t = 30 is when the first 250 mL water is given, on all study days.
Secondary outcome [1] 436670 0
The difference in estimated renal glucose reabsorption between Ace-K and placebo days in healthy participants.
Timepoint [1] 436670 0
Placebo visit and Ace-K visit
Secondary outcome [2] 436671 0
The difference in the amount of glucose infused intravenously to maintain the hyperglycaemic clamp between Ace-K and placebo days in healthy participants:
Timepoint [2] 436671 0
Placebo visit and Ace-K visit
Secondary outcome [3] 436672 0
The difference in plasma insulin levels between Ace-K and placebo days in healthy participants:
Timepoint [3] 436672 0
t =0, 30, 60, 90, 120, 150, 180 and 210 min, where t = 0 is when glucose clamping starts and t = 30 is when the first 250 mL water is given, on study days.

Eligibility
Key inclusion criteria
- Healthy males and females aged from 18 to 70 years
- Body mass index (BMI) from 18 to 30 kg/m2
- HbA1c less than 5.7%
- Fasting blood glucose less than 5.6 mmol/L
Minimum age
18 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Habitual use of more than one serve of any food or beverage containing a low-calorie sweetener per day during the past 3 months, ascertained using a low-calorie sweetener frequency questionnaire.
- Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes on a daily basis
- Haemoglobin below the lower limit of the normal range (ie. < 135 g/L for men and 115 g/L for women), and ferritin below the lower limit of normal (ie. < 30 ng/mL for men and 20 mg/mL for women)
- Female participants who are pregnant or planning for pregnancy, or are lactating
- 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 10 healthy participants will provide at least 80% power (a = 0.05) to detect ~30% difference in urinary glucose excretion over 3 hours. 12 healthy participants will be recruited to allow for drop-outs.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2024
Actual
Date of last participant enrolment
Anticipated
28/02/2025
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 316794 0
Charities/Societies/Foundations
Name [1] 316794 0
The Hospital Research Foundation
Country [1] 316794 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
Country
Australia
Secondary sponsor category [1] 319016 0
None
Name [1] 319016 0
Address [1] 319016 0
Country [1] 319016 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315563 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 315563 0
https://www.rah.sa.gov.au/research/for-researchers/central-adelaide-local-health-network-human-research-ethics-committee
Ethics committee country [1] 315563 0
Australia
Date submitted for ethics approval [1] 315563 0
20/11/2022
Approval date [1] 315563 0
19/05/2024
Ethics approval number [1] 315563 0
2022/HRE00300

Summary
Brief summary
Low-calorie sweeteners (LCS) have been widely used in food and beverages in recent decades. However, a recent World Health Organisation (WHO) report highlighted that people who consume LCS regularly have an increased risk of developing type 2 diabetes (T2D). Acesulfame potassium (Ace-K) is a widely used low-calorie sweetener that is absorbed from the gut and excreted in the urine. We want to find out whether Ace-K consumption reduces the amount of glucose excreted in the urine in healthy humans.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135086 0
A/Prof Tongzhi Wu
Address 135086 0
Level 6 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 135086 0
Australia
Phone 135086 0
+61 8 8313 6535
Fax 135086 0
Email 135086 0
tongzhi.wu@adelaide.edu.au
Contact person for public queries
Name 135087 0
Tongzhi Wu
Address 135087 0
Level 6 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 135087 0
Australia
Phone 135087 0
+61 8 8313 6535
Fax 135087 0
Email 135087 0
tongzhi.wu@adelaide.edu.au
Contact person for scientific queries
Name 135088 0
Tongzhi Wu
Address 135088 0
Level 6 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 135088 0
Australia
Phone 135088 0
+61 8 8313 6535
Fax 135088 0
Email 135088 0
tongzhi.wu@adelaide.edu.au

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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