Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000866505
Ethics application status
Approved
Date submitted
22/07/2015
Date registered
19/08/2015
Date last updated
18/01/2022
Date data sharing statement initially provided
22/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Do artificial sweeteners influence intestinal glucose absorption in humans?
Scientific title
A randomised, double-blind, placebo-controlled trial to determine whether diet supplementation with non-caloric sweeteners alters the rate of intestinal glucose absorption in healthy individuals
Secondary ID [1] 287127 0
Royal Adelaide Hospital Protocol Number: 150605
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 295664 0
Condition category
Condition code
Metabolic and Endocrine 295942 295942 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Healthy subjects will be screened then undergo 2 study day visits in a randomised, double-blinded manner. Study day 1 will occur prior to diet supplementation, with study day 2 immediately following 2 weeks of diet supplementation with placebo capsules or capsules containing a combination of non-caloric sweeteners (sucralose, 92 mg + acesulfame K, 52 mg). Single capsules will be consumed immediately prior to meals, three times daily. Adherence to the intervention will be monitored by capsule return.

On each study day, fasted unsedated subjects will have an intravenous cannula inserted into a forearm vein in one arm for blood sampling and a small diameter (5.3 mm) video endoscope placed in position in the second part of the duodenum via an anaesthetised nostril. Five mucosal biopsies will be collected via endoscope forceps, then an intraduodenal glucose infusion commenced for 30 min via the endoscope channel (30 g glucose, together with 3 g of the non-metabolisable glucose analogue 3-O-methy-glucose (3-OMG) dissolved in water to a total volume of 150 mL, infused at 5 mL/min; 4 kcal/min). An additional 5 biopsies will be collected post-infusion; bloods will be collected regularly over 2 hours.
Intervention code [1] 292398 0
Treatment: Other
Comparator / control treatment
Placebo capsules (hydroxypropyl methylcellulose)
Control group
Placebo

Outcomes
Primary outcome [1] 295643 0
Proportional differences in incremental area under the curve, peak and/or time-to-peak for serum 3-OMG levels (absorption) for sweetener vs. placebo supplementation during intraduodenal glucose infusion (composite outcome)
Timepoint [1] 295643 0
T = -10, 0 (commencement of intraduodenal glucose infusion), 10, 20, 30, 40, 50, 60, 90 and 120 min
Secondary outcome [1] 316067 0
Proportional differences in incremental area under the curve, peak and/or time-to-peak for plasma incretins for sweetener vs. placebo supplementation during intraduodenal glucose infusion (composite outcome)
Timepoint [1] 316067 0
T = -10, 0 (commencement of intraduodenal glucose infusion), 10, 20, 30, 40, 50, 60, 90 and 120 min
Secondary outcome [2] 316068 0
Changes in baseline or post-infusion expression of transcript (RNA) and/or protein for glucose sensing and transport/uptake pathway molecules in mucosal biopsies (composite outcome)

Targets assessed include sweet taste receptors (T1R2, T1R3), G-protein (alpha-gustducin), ion channels (Kir6.2, TRPM5) and glucose transporters (SGLT-1, GLUT2).
Timepoint [2] 316068 0
T = -2 (immediately prior to commencement of intraduodenal glucose infusion) and 30 min
Secondary outcome [3] 316069 0
Identification of glucose sensing, signalling and transport/uptake pathway molecules in functionally activated (glucose-responsive) cells within mucosal biopsies (composite outcome)

Targets assessed include sweet taste receptors (T1R2, T1R3), G-protein (alpha-gustducin), ion channels (Kir6.2, TRPM5), glucose transporters (SGLT-1, GLUT2) and cell markers (5-HT, GLP-1, GIP)
Timepoint [3] 316069 0
T = 30 min, where T=0 is the start of glucose infusion
Secondary outcome [4] 405082 0
Changes in taxonomic and functional gut microbial features after placebo vs. sweetener supplementation and their relationship to outcomes in subjects, assessed by stool sample analysis and statistical modelling.
Timepoint [4] 405082 0
Changes in gut microbiota in stool samples collected after overnight fast on study days before and after placebo vs. sweetener supplementation.

Eligibility
Key inclusion criteria
Non-diabetic, healthy volunteers matched as closely as possible for sex and body mass index; Body mass index 20-30 kg/m2; HbA1c less than or equal to 7.0%
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Significant illness including impairment to cardiovascular or respiratory function that would limit a subject’s activity and therefore would represent a risk to undertaking endoscopy safely (American Society of Anaesthesiologists Grade 3 or more); History of gastrointestinal disease, including significant upper gastrointestinal symptoms (assessed by a validated gastrointestinal symptom questionnaire), pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendectomy or cholecystectomy); Diffuse mucosal disease involving the upper gastrointestinal tract, including Crohn’s disease, coeliac disease, or ischaemic changes, evident either macroscopically or on histopathological examination of mucosal biopsies; Haemoglobin below the lower limit of the normal range (ie. below 135g/L for men and 115g/L for women), and ferritin below the lower limit of normal (below 20ng/mL for women and 30ng/mL for men); Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests, > 2 times upper limit of normal); Body mass index > 30 kg/m2 or < 20 kg/m2; Donation of blood within the previous 3 months; Participation in any other research studies within the previous 3 months; Subjects requiring the use of anticoagulant drugs, antiplatelet agents or NSAIDS; Subjects with known coagulopathy; Presence of mucosal abnormalities at endoscopy; Subjects requiring medication that may influence gastrointestinal function; Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes per day; Female patients not using appropriate contraceptive method (ie oral contraceptive pill, diaphragm, DepoProvera hormonal contraceptive injection, intrauterine device (IUD), Norplant method); Vegetarian, lactation or pregnancy (verified by urine testing in women of reproductive age; in these subjects, study will be completed during the follicular phase of the menstrual cycle); habitual consumption of >500 mL of artificially sweetened drink, or food equivalent

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Potential participants will be screened for medical and diet history, medications and lifestyle as well as assessed for blood haemoglobin, ferritin, HbA1c, renal and liver function. Study participants will provide written, informed consent and will be randomised and blinded to placebo or sweetener capsules. Study capsules will be identical in size, colour and weight.

Allocation concealment by schedule will be undertaken and held by pharmacy staff of the Royal Adelaide Hospital; allocation will be blind to staff and subjects involved in this project.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer-generated random number table
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
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample sizes are calculated for alpha=0.05 and beta=0.2 from a priori data on the primary outcome measures. The effect size for glucose absorption, the most variable outcome, is 1.052; subject dropouts are incorporated at 15%. All variables will be assessed using ANOVA, with treatment and time factors. Post hoc tests, adjusted for multiple comparisons, will be performed for significant effects. Relationships between transcript expression and other factors will be compared using Pearson correlation coefficient; area-under-the-curve data will be compared using 2-tailed paired Student’s t-tests.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/09/2015
Actual
10/09/2015
Date of last participant enrolment
Anticipated
Actual
26/04/2017
Date of last data collection
Anticipated
Actual
15/08/2020
Sample size
Target
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 291694 0
Government body
Name [1] 291694 0
National Health & Medical Research Council
Country [1] 291694 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
North Terrace
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 290369 0
None
Name [1] 290369 0
Address [1] 290369 0
Country [1] 290369 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293221 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 293221 0
Ethics committee country [1] 293221 0
Australia
Date submitted for ethics approval [1] 293221 0
Approval date [1] 293221 0
02/07/2015
Ethics approval number [1] 293221 0
HREC/15/RAH/223, Protocol 150605

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

Contacts
Principal investigator
Name 58922 0
A/Prof Richard L Young
Address 58922 0
Discipline of Medicine, University of Adelaide
Level 3, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace, Adelaide SA 5000
Country 58922 0
Australia
Phone 58922 0
+61 8 82222082
Fax 58922 0
+61 8 82223870
Email 58922 0
[email protected]
Contact person for public queries
Name 58923 0
Richard L Young
Address 58923 0
Discipline of Medicine, University of Adelaide
Level 3, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace, Adelaide SA 5000
Country 58923 0
Australia
Phone 58923 0
+61882222082
Fax 58923 0
+61 8 82223870
Email 58923 0
[email protected]
Contact person for scientific queries
Name 58924 0
Richard L Young
Address 58924 0
Discipline of Medicine, University of Adelaide
Level 3, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace, Adelaide SA 5000
Country 58924 0
Australia
Phone 58924 0
+61 8 82222082
Fax 58924 0
+61 8 82223870
Email 58924 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
De-identified participant data used as a criteria of study enrolment


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.