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Trial registered on ANZCTR


Registration number
ACTRN12619000413123
Ethics application status
Approved
Date submitted
21/02/2019
Date registered
13/03/2019
Date last updated
10/06/2021
Date data sharing statement initially provided
13/03/2019
Date results provided
10/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of intragastric administration of L-leucine and L-isoleucine on gastric emptying, gut hormone release and blood glucose in normal weight, overweight or obese type 2 diabetic patients.
Scientific title
Effects of intragastric administration of L-leucine and L-isoleucine on gastric emptying, gut hormone release and blood glucose in normal weight, overweight or obese type 2 diabetic patients.
Secondary ID [1] 297098 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes
 311110 0
Obesity 311686 0
Condition category
Condition code
Diet and Nutrition 309740 309740 0 0
Obesity
Metabolic and Endocrine 309741 309741 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Assessment of blood glucose and gastric emptying,
following administration of control, or 10g L-Leucine, or 10g L-Isoleucine 30 min prior to a standardised mixed nutrient drink.

Subjects will receive, in randomized, double-blind fashion: i) an intragastric bolus infusion of 10g L-Leucine (100ml); ii) an intragastric bolus infusion of 10g L-Isoleucine (100ml); iii) an intragastric bolus infusion of saline (control) (100ml). Subjects will receive one infusion per visit. All bolus infusion will be administered by the primary researcher. Study visits will be separated by 3-7 days. In addition, during study visits, the primary researcher will be present in order to closely monitor adherence to study protocol.

For each study visit a baseline blood sample, VAS, and breath sample will be collected (t = -31). At t = -31 the infusion will be administered over 1 minute using a feeding tube. At t = -20, -10, and -1 min further blood samples will be collected and VAS completed. At t = -1 min, subjects will consume, within 1 minute, a mixed-nutrient drink (Resource Plus, 500 kcal, 325 ml) labeled with 100 mg of 13C-acetate for measurement of gastric emptying by breath sampling, and 3g 3-OMG for measurement of glucose absorption. Blood samples and VAS will be taken every 15 minutes, and breath samples will be taken every 5 min, over the next hour (t = 0 to 60 min). Over the following hour, VAS and blood samples will be collected every half hour (t = 90, 120), and breath samples collected every 15 min (t = 75, 90, 105, 120).

Intervention code [1] 313369 0
Treatment: Other
Comparator / control treatment
Saline control (administered intragastrically) for within group comparison.
Control group
Placebo

Outcomes
Primary outcome [1] 318703 0
Blood glucose response to the mixed nutrient Resource Plus drink.

Timepoint [1] 318703 0
Blood glucose will be assessed from blood samples taken at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, 120 min, where t = -31 is just prior to the time of L-Leucine or L-isoleucine administration and t = -1 is just prior to nutrient drink consumption.
Secondary outcome [1] 365772 0
Gastric emptying (measurement of 13CO2 in breath samples).
Timepoint [1] 365772 0
Breath samples will be collected at t = -31 min, every 5 minutes from t = 0 to 60 min, and every 15 minutes from t = 60 to 120 min.
Secondary outcome [2] 365773 0
Plasma concentrations of gastrointestinal hormones (e.g. GLP-1, GIP ), insulin, glucose and 3-OMG.
(composite secondary outcome)
Timepoint [2] 365773 0
Gut hormone release will be assessed from blood samples taken at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min.
Secondary outcome [3] 367272 0
Appetite perceptions using a VAS questionnaire: hunger.
Timepoint [3] 367272 0
VAS questionnaires will be completed at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min.
Secondary outcome [4] 367379 0
Appetite perceptions using a VAS questionnaire: fullness.
Timepoint [4] 367379 0
VAS questionnaires will be completed at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min.
Secondary outcome [5] 367381 0
Appetite perceptions using a VAS questionnaire: desire to eat.
Timepoint [5] 367381 0
VAS questionnaires will be completed at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min.
Secondary outcome [6] 367382 0
Appetite perceptions using a VAS questionnaire: amount of food desired to eat.
Timepoint [6] 367382 0
VAS questionnaires will be completed at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min.

Eligibility
Key inclusion criteria
A total of 14 lean, overweight or obese T2DM (BMI 19-37 kg/m2) male and female subjects, aged between 18 - 70 years, will be included in the study. T2DM diagnosis will be based on WHO criteria (i.e. HbA1c will be >=6.5 - <=7.9%). Patients will be diet-controlled or required to cease oral blood glucose lowering medication 48 hours before participatiing in the study. All subjects will be required to be weight stable (ie <5% fluctuation) at study entry, which will be ascertained by a stable body weight in the preceeding 4 weeks. Subjects will be required to maintain their normal physical activity over the course of the study, which will be assessed using diaries. Females will be required to be postmenopausal.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Significant gastrointestinal symptoms, disease or surgery;
Use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, gastrointestinal function, body weight or appetite (eg domperidone and cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.)
Lactose intolerance/other food allergy(ies)
Current gallbladder or pancreatic disease
Cardiovascular or respiratory diseases
Those with low ferritin levels (less than 30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study
Any other illnesses as assessed by the investigator (including chronic illnesses not explicitly listed above)
High performance athletes
Current intake of greater than 2 standard drinks on greater than 5 days per week
Current smokers of cigarettes/cigars/marijuana
Current intake of any illicit substance
Vegetarians
Inability to comprehend study protocol
Restrained eaters (score >12 on the three factor eating questionnaire). The degree of eating restraint will be assessed for all, but not used as an exclusion criteria for overweight or obese subjects, as overweight and obese often have some degree of eating restraint
HbA1c <6.5% - >7.9%; metformin medication >2g/d
Estimated glomerular filtration rate <45ml/min

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 subject number and randomised treatment for each study visit. Randomisation involves contacting the holder (study assistant) of the randomisation table to inform them of the next subjects details and study dates. The unblinded study assistant is therefore responsible for allocating a random treatment to the subject and preparing the solution on each study day.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation is generated using a randomization 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
Bio-availability
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/03/2019
Actual
20/03/2019
Date of last participant enrolment
Anticipated
9/12/2019
Actual
4/09/2019
Date of last data collection
Anticipated
20/12/2019
Actual
19/09/2019
Sample size
Target
12
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 301665 0
Government body
Name [1] 301665 0
NHMRC
Country [1] 301665 0
Australia
Primary sponsor type
Individual
Name
Christine Feinle-Bisset
Address
Discipline of Medicine
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] 301379 0
Individual
Name [1] 301379 0
Michael Horowitz
Address [1] 301379 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce
Adelaide, SA 5005
Country [1] 301379 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302385 0
Central Adelaide Local Health Network Research Ethics Committee
Ethics committee address [1] 302385 0
Ethics committee country [1] 302385 0
Australia
Date submitted for ethics approval [1] 302385 0
27/06/2014
Approval date [1] 302385 0
30/06/2014
Ethics approval number [1] 302385 0
HREC/14/RAH/286

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

Contacts
Principal investigator
Name 90050 0
Prof Chrisitine Feinle-Bisset
Address 90050 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce
Adelaide, SA 5005
Country 90050 0
Australia
Phone 90050 0
+61 8 8313 6053
Fax 90050 0
Email 90050 0
christine.feinle@adelaide.edu.au
Contact person for public queries
Name 90051 0
Penelope Fitzgerald
Address 90051 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce
Adelaide, SA 5005
Country 90051 0
Australia
Phone 90051 0
+61 8 8313 6278
Fax 90051 0
Email 90051 0
penelope.fitzgerald@adelaide.edu.au
Contact person for scientific queries
Name 90052 0
Chrisitine Feinle-Bisset
Address 90052 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce
Adelaide, SA 5005
Country 90052 0
Australia
Phone 90052 0
+61 8 8313 6053
Fax 90052 0
Email 90052 0
christine.feinle@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
To align with intellectual property agreement.


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.