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Trial registered on ANZCTR


Registration number
ACTRN12621000981820
Ethics application status
Approved
Date submitted
28/05/2021
Date registered
26/07/2021
Date last updated
26/07/2021
Date data sharing statement initially provided
26/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating whether blocking intestinal sweet taste sensing alters blood glucose control in adults with type 2 diabetes
Scientific title
A double-blinded placebo-controlled parallel design trial to determine whether inhibiting intestinal sweet taste sensing improves glycaemic responses in patients with type 2 diabetes
Secondary ID [1] 304337 0
Nil known
Universal Trial Number (UTN)
U1111-1267-7526
Trial acronym
BOLSTER
Linked study record
The current study is a follow up of ACTRN12615000948594 with a chronic rather than acute lactisole exposure setting.

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 322094 0
Condition category
Condition code
Metabolic and Endocrine 319810 319810 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with Type 2 Diabetes Mellitus will be screened then undergo two study day visits in a randomised, double-blinded manner. Study day one will occur prior to diet supplementation, with study day two immediately following four weeks of diet supplementation with placebo capsules or capsules containing the sweet taste blocker, lactisole (300mg). Single capsules will be consumed immediately prior to meals, three times daily. Adherence to intervention will be monitored by capsule return and patient diary.

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 silicone rubber nasoenteral catheter positioned into the second part of the duodenum via an anaesthetised nostril as confirmed by transmucosal potential difference. An intraduodenal glucose infusion will be commenced for 30 min via the catheter (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). Bloods will be collected regularly over 2 hours; stool will be collected pre and post study for microbiome analyses.
Intervention code [1] 320692 0
Treatment: Other
Comparator / control treatment
Adherence to placebo treatment (microcellulose) will be monitored by capsule return and patient diary.
Control group
Placebo

Outcomes
Primary outcome [1] 327681 0
Proportional increase in the incremental area under the curve (iAUC), peak and/or time-to-peak for serum 3-OMG levels (absorption) for lactisole vs. placebo supplementation during intraduodenal glucose infusion
Timepoint [1] 327681 0
Study visit 1, T = -10, 0, 10, 20, 30, 40, 50, 60, 90 and 120 min (primary timepoint) during (T = 0-30) and post-glucose challenge pre-study, and study visit 2, T = -10, 0, 10, 20, 30, 40, 50, 60, 90 and 120 min (primary timepoint) during (T = 0-30) and post-glucose challenge after 4 weeks of supplementation post-study.
Primary outcome [2] 327682 0
Proportional increase in the incremental area under the curve (iAUC), peak and/or time-to-peak for blood glucose for lactisole vs. placebo supplementation during intraduodenal glucose infusion
Timepoint [2] 327682 0
Study visit 1, T = -10, 0, 10, 20, 30, 40, 50, 60, 90 and 120 min (primary timepoint) during (T = 0-30) and post-glucose challenge pre-study, and study visit 2, T = -10, 0, 10, 20, 30, 40, 50, 60, 90 and 120 min (primary timepoint) during (T = 0-30) and post-glucose challenge after 4 weeks of supplementation post-study.
Secondary outcome [1] 396212 0
Composite outcome of proportional increase in the iAUC, peak and/or time-to-peak for serum 1,5-AG levels for lactisole vs. placebo supplementation during intraduodenal glucose infusion
Timepoint [1] 396212 0
Study visit 1, T = -10, 0, 10, 20, 30, 40, 50, 60, 90 and 120 min during (T = 0-30) and post-glucose challenge pre-study, and study visit 2, T = -10, 0, 10, 20, 30, 40, 50, 60, 90 and 120 min during (T = 0-30) and post-glucose challenge after 4 weeks of supplementation post-study.
Secondary outcome [2] 396213 0
Composite outcome of proportional increase in the iAUC, peak and/or time-to-peak for plasma gut hormone levels for lactisole vs. placebo supplementation during intraduodenal glucose infusion
Timepoint [2] 396213 0
Study visit 1, T = -10, 0, 10, 20, 30, 40, 50, 60, 90 and 120 min during (T = 0-30) and post-glucose challenge pre-study, and study visit 2, T = -10, 0, 10, 20, 30, 40, 50, 60, 90 and 120 min during (T = 0-30) and post-glucose challenge after 4 weeks of supplementation post-study.
Secondary outcome [3] 396214 0
Exploratory changes in taxonomic and functional microbiome characteristics assessed by shotgun RNA sequencing of stool samples.
Timepoint [3] 396214 0
Stool samples collected from study participant at 0800 on each study day morning pre-supplementation and 4 weeks post-supplementation

Eligibility
Key inclusion criteria
i) Volunteers with Type 2 Diabetes Mellitus (American Diabetes Association criteria) managed by metformin alone (morning dose of metformin will be withheld until after study day lunch on each visit, to reduce effects on gut hormone responses)
ii) HbA1c less than or equal to 8.5%
iii) Body mass index (BMI) 25 - 35 kg/m2
iv) Haemoglobin above the lower limit of the normal range (i.e. above 135g/L for men and above 115g/L for women), and ferritin above the lower limit of normal (above 20ng/mL for women and above 30ng/mL for men)
v) Consumption of more than one low-calorie sweetener (LCS) containing beverage per day, or equivalent
Minimum age
40 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i) Significant illness, other than type 2 diabetes, including impairment to cardiovascular or respiratory function that limits a participant’s activity and represents a risk to safe placement of a nasoenteral catheter.
ii) History of gastrointestinal disease, including significant upper gastrointestinal symptoms (assessed by validated gastrointestinal symptom questionnaire), pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendectomy or cholecystectomy)
iii) Impaired renal or liver function (as assessed by calculated creatinine clearance less than or equal to 90 mL/min or abnormal liver function tests (greater than or equal to 2 times upper limit of normal))
iv) Participants medicated with anti-diabetics other than metformin
v) Participants unable to self-monitor blood glucose levels
vi) Volunteers with body mass index greater than or equal to 20 kg/m2 or less than or equal to 35 kg/m2
vii) Donation of blood within the previous 3 months
viii) Participation in any other research studies within the previous 3 months
ix) Participants medicated with opiates, anticholinergics, levodopa, clonidine, nitrates, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, prucalopride, or erythromycin
x) Evidence of drug abuse, daily consumption of more than 20 g alcohol or 10 cigarettes
xi) Female patients not using appropriate contraceptive method (i.e. oral contraceptive pill, diaphragm, DepoProvera hormonal contraceptive injection, intrauterine device, Norplant method)
xii) Vegetarian, lactation, or pregnancy

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)
Allocation will involve contacting the holder of the allocation schedule who was off-site at a central administration site
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated random number table (Sealed Envelope®, London, UK)
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
Samples sizes provide over 80% power to detect a 25% difference in incremental area-under-the-curve, iAUC0-120 min, for the glycaemic response to enteral glucose between lactisole and placebo in a parallel design, and are based on a priori data in ACTRN12615000948594.

Forty T2D patients (N = 20 each) will be recruited, allowing for a 15% drop-out rate. Sample sizes are based on a=0.05 and ß=0.2 for variability in glycaemic responses in a priori studies. Statistical analyses of physiological variables will be analysed per protocol model using ANCOVA, with adjustment for baseline values; post hoc tests, adjusted for multiple comparisons will be performed as indicated

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/08/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 19590 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 34197 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 308709 0
Charities/Societies/Foundations
Name [1] 308709 0
Diabetes Australia
Country [1] 308709 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
North Terrace, Adelaide South Australia 5000
Country
Australia
Secondary sponsor category [1] 309609 0
None
Name [1] 309609 0
Address [1] 309609 0
Country [1] 309609 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308633 0
Central Adelaide Local Health Network
Ethics committee address [1] 308633 0
Ethics committee country [1] 308633 0
Australia
Date submitted for ethics approval [1] 308633 0
06/05/2021
Approval date [1] 308633 0
20/05/2021
Ethics approval number [1] 308633 0
2021/HRE00157

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

Contacts
Principal investigator
Name 111378 0
A/Prof Richard L Young
Address 111378 0
Lifelong Health, South Australian Health & Medical Research Institute Nutrition & Metabolism North Terrace, Adelaide SA 5000
Country 111378 0
Australia
Phone 111378 0
+61 8 8128 4845
Fax 111378 0
Email 111378 0
richard.young@adelaide.edu.au
Contact person for public queries
Name 111379 0
Richard L Young
Address 111379 0
Lifelong Health, South Australian Health & Medical Research Institute Nutrition & Metabolism North Terrace, Adelaide SA 5000
Country 111379 0
Australia
Phone 111379 0
+61 8 8128 4845
Fax 111379 0
Email 111379 0
richard.young@adelaide.edu.au
Contact person for scientific queries
Name 111380 0
Richard L Young
Address 111380 0
Lifelong Health, South Australian Health & Medical Research Institute Nutrition & Metabolism North Terrace, Adelaide SA 5000
Country 111380 0
Australia
Phone 111380 0
+61 8 8128 4845
Fax 111380 0
Email 111380 0
richard.young@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

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

Documents added automatically
No additional documents have been identified.