Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000778684
Ethics application status
Approved
Date submitted
26/06/2023
Date registered
18/07/2023
Date last updated
10/05/2024
Date data sharing statement initially provided
18/07/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of combined administration of L-tryptophan and lauric acid on gut functions, and blood glucose control in humans with type 2 diabetes
Scientific title
Effects of combined administration of L-tryptophan and lauric acid on gastric emptying of, and the gut and glucoregulatory hormone and postprandial blood glucose responses to, a mixed-nutrient drink in humans with type 2 diabetes
Secondary ID [1] 309836 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 330265 0
Obesity 330266 0
Condition category
Condition code
Metabolic and Endocrine 327133 327133 0 0
Diabetes
Diet and Nutrition 327134 327134 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive in a randomised, double-blind fashion, a 45-min intraduodenal infusion of either (i) L-tryptophan at 0.10 kcal/min (1.1 g/45 min), (ii) lauric acid at 0.3 kcal/min (1.5 g/45 min), (iii) combination of (i) and (ii), or (iv) saline (control) on 4 separate visits. The total duration of each study visit will be 4.5-6 hours, and will be separated by 3-7 days. To ensure adherence to the intervention, research staff will closely supervise the participants throughout the study visit. Study visits will be performed in the Clinical Research Facility of the Adelaide Medical School, by University of Adelaide staff and students trained in the required techniques.

Participants will consume a standardised dinner meal, (400g McCain's beef lasagne), the night before each study visit between 6:30 to 7 pm. After being fasted for 13.5 to 14 hrs overnight and refraining from any exercise and alcohol intake for 24 hrs, participants will arrive at the laboratory at 8:30 am. Upon arrival, participants will be intubated with a 17-channel manometric catheter that will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The manometric catheter consists of 16 side holes spaced at 1.5 cm intervals and an additional channel (with the side hole positioned approx. 14 cm distal to the pylorus when the catheter is in the correct position) is used for intraduodenal infusions. The correct positioning of the catheter will be maintained by continuous measurement of the transmucosal potential difference (TMPD) between the most distal antral channel and the most proximal duodenal channel. Once the catheter has been positioned correctly, an intravenous cannula will be placed into a forearm vein for blood sampling.

At t = -31 min, a baseline blood sample and breath sample will be taken, and participants will complete a visual analogue scale (VAS) questionnaire. Immediately thereafter (t = -30 min), one of the infusions will commence, and continue until t = 15 min. At t = -1 min, participants will be given a mixed-nutrient drink (containing 500 kcal, 74 g carbohydrates) to consume within 2 min, which will be marked with carbon-13 acetate to facilitate the measurement of gastric emptying using 13C-breath test. Blood samples, VAS
ratings and breath samples will be obtained at regular intervals until t = 180 min. Participants will then be served a light lunch, consisting of a sandwich, fruit/muesli bar, and water, and then allowed to leave the laboratory.
Intervention code [1] 326267 0
Treatment: Other
Comparator / control treatment
Saline (sodium chloride 0.9%)
Control group
Placebo

Outcomes
Primary outcome [1] 335004 0
Changes in plasma glucose concentration
Timepoint [1] 335004 0
Plasma will be obtained from blood samples taken at t = -31, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180 min, where t = -31 is just prior to infusion commencement and t = 180 is 180 mins following ingestion of the mixed-nutrient drink.
Primary outcome [2] 335005 0
Changes in C-peptide, and other gut hormone concentrations, including cholecystokinin, GLP-1 and GIP, This outcome is of an exploratory nature so that other gut hormones to be measured may be decided upon based on the effects of this intervention on plasma glucose, and other outcomes.
Timepoint [2] 335005 0
Plasma will be obtained from blood samples taken at t = -31, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180 min, where t = -31 is just prior to infusion commencement and t = 180 is 180 mins following ingestion of the mixed-nutrient drink.
Primary outcome [3] 335006 0
Gastric emptying will be measured using a 13C-acetate breath test, measuring
13CO2 concentrations in exhaled air of end-expiratory breath samples.
Timepoint [3] 335006 0
Breath samples will be collected at t = -31, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180 min,, where t = -31 is just prior to infusion commencement and t = 180 is 180 mins following ingestion of the mixed-nutrient drink.
Secondary outcome [1] 422686 0
Appetite ratings (hunger, fullness, desire to eat, and prospective consumption), GI symptoms (nausea and bloating) and drowsiness will be assessed using a 100mm visual analogue scale (VAS) questionnaire. This VAS has been extensively employed in published studies conducted by the investigators. This outcome is of an exploratory nature so that specific parameters to be measured may be decided upon based on the effect of the intervention on this and other outcomes, therefore, this is a composite outcome.
Timepoint [1] 422686 0
VAS questionnaires will be completed at t = -31, -15, 0, 10, 20, 30, 45, 60, 75, 90, 105, 120, 150, 180 min, where t = -31 is just prior to infusion commencement and t = 180 is 180 mins following ingestion of the mixed-nutrient drink.

Eligibility
Key inclusion criteria
Male participants with type 2 diabetes mellitus (T2DM), (aged 18-75 years BMI: 28-38 kg/m2), will be included in the study. T2DM diagnosis will be based on WHO criteria. HbA1c will be >=6.5 - <=7.9% at screening. Blood glucose medications will be required to be withheld for 48 hours prior to each study day. All participants will be required to be weight-stable (ie <5% fluctuation) at study entry, which will be ascertained by a stable body weight in the preceding 4 weeks.
Minimum age
18 Years
Maximum age
75 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Significant GI symptoms, or history of GI disease or surgery
Current gallbladder or pancreatic disease
Cardiovascular or respiratory diseases
Any other illnesses (except type 2 diabetes) as assessed by the investigator (including chronic illnesses not explicitly listed above)
Use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, GI function, bodyweight or appetite (e.g. domperidone, cisapride, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.)
Lactose intolerance/other food allergy(ies)
Individuals with low ferritin levels (<30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study
High performance athletes
Current intake of > 2 standard drinks on > 5 days per week (>140g/week)
Current smokers of tobacco (cigarettes, cigars, pipes, sheesha, chewing, vaping etc.)
Current use of recreational drugs, e.g. marijuana
Current intake of any illicit substance
Vegetarians
Inability to tolerate nasoduodenal tube
Inability to comprehend study protocol
HbA1c <6% or >7.9%
Estimated glomerular filtration rate <45 ml/min
Any patient whose medication cannot be withheld for 48 hours for medical reasons

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)
Eligible volunteers are assigned a participant number and randomised treatment for each study visit. Randomisation involves contacting the holder (study assistant) of the randomisation table to inform them of participants details and study dates. The unblinded study assistant is, therefore, responsible for allocating a random treatment to the participant and preparing the treatment on each study day.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation is generated using a randomisation plan generator available at www.randomization.com
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
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
24/07/2023
Actual
6/09/2023
Date of last participant enrolment
Anticipated
31/07/2024
Actual
Date of last data collection
Anticipated
31/08/2024
Actual
Sample size
Target
15
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 314020 0
Government body
Name [1] 314020 0
National Health and Medical Research Council (NHMRC)
Country [1] 314020 0
Australia
Funding source category [2] 314023 0
Charities/Societies/Foundations
Name [2] 314023 0
Diabetes Australia
Country [2] 314023 0
Australia
Primary sponsor type
Individual
Name
Christine Feinle-Bisset
Address
Adelaide Medical School
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce,
Adelaide, SA 5005
Country
Australia
Secondary sponsor category [1] 315909 0
Individual
Name [1] 315909 0
Michael Horowitz
Address [1] 315909 0
Adelaide Medical School
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce,
Adelaide, SA 5005
Country [1] 315909 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313156 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 313156 0
Ethics committee country [1] 313156 0
Australia
Date submitted for ethics approval [1] 313156 0
06/06/2019
Approval date [1] 313156 0
18/06/2019
Ethics approval number [1] 313156 0
R20130611

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

Contacts
Principal investigator
Name 127190 0
Prof Christine Feinle-Bisset
Address 127190 0
School of Medicine, University of Adelaide
Level 5, AHMS Building
4 North Terrace
Adelaide SA 5005
Country 127190 0
Australia
Phone 127190 0
+61 8 83136053
Fax 127190 0
Email 127190 0
[email protected]
Contact person for public queries
Name 127191 0
Penelope Fitzgerald
Address 127191 0
School of Medicine, University of Adelaide
Level 5, AHMS Building
4 North Terrace
Adelaide SA 5005
Country 127191 0
Australia
Phone 127191 0
+61 8 83136278
Fax 127191 0
Email 127191 0
[email protected]
Contact person for scientific queries
Name 127192 0
Christine Feinle-Bisset
Address 127192 0
School of Medicine, University of Adelaide
Level 5, AHMS Building
4 North Terrace
Adelaide SA 5005
Country 127192 0
Australia
Phone 127192 0
+61 8 83136053
Fax 127192 0
Email 127192 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 datasets generated during and/or analysed during the current study are not publicly available due to the ethical statement and informed consent that require privacy of data.


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.