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Trial registered on ANZCTR


Registration number
ACTRN12624000377538
Ethics application status
Approved
Date submitted
7/03/2024
Date registered
2/04/2024
Date last updated
2/04/2024
Date data sharing statement initially provided
2/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Development of a novel bile acid-based therapy to optimise postprandial glycaemic control in type 2 diabetes
Scientific title
Development of a novel bile acid-based therapy to optimise postprandial glycaemic control in people with type 2 diabetes
Secondary ID [1] 311670 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 333130 0
Obesity 333131 0
Condition category
Condition code
Metabolic and Endocrine 329827 329827 0 0
Diabetes
Diet and Nutrition 329828 329828 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following enrolment, each participant will be studied on 5 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 until the following morning (except that water will be allowed until 10 pm), when they will attend the Clinical Research Facility (CRF) of the Adelaide Health and Medical Science (AHMS) building at ~0800h. The participant will receive a text message the evening before the study day to remind them to have the standardised meal and stay fasting until the following morning.

On each study day, participants will be instructed to defer any morning dose of prescribed medications until the end of the investigation. Upon arrival, an intravenous cannula will be placed into a vein on the dorsum of the hand, which will be kept warm with a heat pad to allow sampling of “arterialised” blood. Then participants will ingest 4 gelatin capsules, monitored by the investigator, each containing either

(i) placebo (cellulose only);
(ii) 0.5 g taurocholic acid (TCA) - total dose 2 g TCA;
(iii) 0.25 g TCA + 7.5 mg denatonium benzoate (DB) - total dose 1 g TCA + 30 mg DB;
(iv) 0.5 g TCA + 7.5 mg DB - total dose 2 g TCA + 30 mg DB; or
(v) 1 g TCA + 7.5 mg DB - total dose 4 g TCA + 30 mg DB,
with 150 mL water (t = -30 min).

At t = 0 min, participants will consume a mashed potato meal comprising 65 g powdered potato (Continental, Epping, NSW), 20 g glucose and 20 g margarine reconstituted with 200 mL boiling water and one egg yolk containing 100 uL 13C-octanioc acid (between t = -5 to 0 min).

Breath samples will be collected every 5 min in the first 30 min and every 15 min between t = 30-180 min for the measurement of gastric emptying. “Arterialised” venous blood will be sampled at t = -30, 0, 30, 60, 90, 120, 180 and 240 min for measurement of plasma glucose, glucagon-like peptide-1 (GLP-1), fibroblast growth factor 19 (FGF-19), Serotonin (5-hydroxytryptamine, 5-HT), insulin, C-peptide, glucagon and bile acid profiles. Blood pressure will be monitored every 15 min between t = -30-240 min. The volume of the gallbladder will be measured by 3D ultrasound at t = -30, 0, 30, 60, 90, 120, 150, 180, 210 and 240 min. Gastrointestinal symptoms (e.g. nausea) and appetite sensations (e.g. hunger, fullness) will assessed every 30 min using the standardised visual analogue scales.

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 5 study visits will be 410 mL.
Intervention code [1] 328134 0
Treatment: Drugs
Comparator / control treatment
Microcrystalline cellulose capsule
Control group
Placebo

Outcomes
Primary outcome [1] 337596 0
The difference in plasma glucose (incremental area under the curve (iAUC) from 0 to 240 min) between treatments.
Timepoint [1] 337596 0
t = -30, 0, 30, 60, 90, 120, 150, 180 and 240 min on each study day.
t = -30 is when capsules containing the study drug or placebo were given and t = 0 is when the mashed potato meal is given.
Secondary outcome [1] 432452 0
The difference in gastric half-emptying time between treatments.
Timepoint [1] 432452 0
t = -2, 5, 10, 15, 20, 25, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210, 235 and 240 min on each study day.
t = 0 is when the mashed potato meal is given.
Secondary outcome [2] 432453 0
The difference in gallbladder volume from t = -30 to 240 min between treatments.
Timepoint [2] 432453 0
t = -30, 0, 30, 60, 90, 120, 150, 180, 210 and 240 min.
t = -30 is when capsules containing the study drug or placebo were given and t = 0 is when the mashed potato meal is given.
Secondary outcome [3] 432454 0
The difference in plasma total GLP-1 iAUC from 0 to 240 min between treatments.
Timepoint [3] 432454 0
t = -30, 0, 30, 60, 90, 120, 150, 180 and 240 min on each study day.
t = -30 is when capsules containing the study drug or placebo were given and t = 0 is when the mashed potato meal is given.
Secondary outcome [4] 432455 0
The difference in plasma insulin iAUC from 0 to 240 min between treatments.
Timepoint [4] 432455 0
t = -30, 0, 30, 60, 90, 120, 150, 180 and 240 min on each study day.
t = -30 is when capsules containing the study drug or placebo were given and t = 0 is when the mashed potato meal is given.
Secondary outcome [5] 432456 0
The difference in plasma FGF-19 iAUC from 0 to 240 min between treatments.
Timepoint [5] 432456 0
t = -30, 0, 30, 60, 90, 120, 150, 180 and 240 min on each study day.
t = -30 is when capsules containing the study drug or placebo were given and t = 0 is when the mashed potato meal is given.
Secondary outcome [6] 432457 0
The difference in plasma 5-HT iAUC from 0 to 240 min between treatments.
Timepoint [6] 432457 0
t = -30, 0, 30, 60, 90, 120, 150, 180 and 240 min on each study day.
t = -30 is when capsules containing the study drug or placebo were given and t = 0 is when the mashed potato meal is given.
Secondary outcome [7] 432458 0
The difference in plasma C-peptide iAUC from 0 to 240 min between treatments.
Timepoint [7] 432458 0
t = -30, 0, 30, 60, 90, 120, 150, 180 and 240 min on each study day.
t = -30 is when capsules containing the study drug or placebo were given and t = 0 is when the mashed potato meal is given.
Secondary outcome [8] 432459 0
The difference in plasma glucagon iAUC from 0 to 240 min between treatments.
Timepoint [8] 432459 0
t = -30, 0, 30, 60, 90, 120, 150, 180 and 240 min on each study day.
t = -30 is when capsules containing the study drug or placebo were given and t = 0 is when the mashed potato meal is given.
Secondary outcome [9] 432460 0
Differences in plasma bile acid profiles between study days after GLY-200 and placebo treatment.
Timepoint [9] 432460 0
t = -30, 0, 30, 60, 90, 120, 150, 180 and 240 min on each study day.
t = -30 is when capsules containing the study drug or placebo were given and t = 0 is when the mashed potato meal is given.

Eligibility
Key inclusion criteria
• Type 2 diabetes (American Diabetes Association criteria) treated by diet and/or metformin alone
• Body mass index (BMI) from 20 to 40 kg/m2
• Males and females, aged from 18 to 79 years
• Glycated haemoglobin (HbA1c) from 6.0% to 8.5%
• 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 ng/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
• Use of any medication that may influence gastrointestinal motor function, body weight or appetite (opiates, anticholinergics, levodopa, clonidine, nitrates, tricyclic antidepressants, selective serotonin re-uptake inhibitors, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, prucalopride, or erythromycin)
• History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy), or coagulation abnormalities
• 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
• Vegan/vegetarian
• 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 phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer 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
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 315998 0
Government body
Name [1] 315998 0
Diabetes Australia
Country [1] 315998 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
Country
Australia
Secondary sponsor category [1] 318147 0
None
Name [1] 318147 0
Address [1] 318147 0
Country [1] 318147 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314824 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 314824 0
Ethics committee country [1] 314824 0
Australia
Date submitted for ethics approval [1] 314824 0
20/11/2023
Approval date [1] 314824 0
05/03/2024
Ethics approval number [1] 314824 0
2023/HRE00327

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

Contacts
Principal investigator
Name 132838 0
Dr Cong Xie
Address 132838 0
Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 132838 0
Australia
Phone 132838 0
+61 406 167 990
Fax 132838 0
Email 132838 0
[email protected]
Contact person for public queries
Name 132839 0
Cong Xie
Address 132839 0
Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 132839 0
Australia
Phone 132839 0
+61 406 167 990
Fax 132839 0
Email 132839 0
[email protected]
Contact person for scientific queries
Name 132840 0
Cong Xie
Address 132840 0
Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 132840 0
Australia
Phone 132840 0
+61 406 167 990
Fax 132840 0
Email 132840 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.