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Trial registered on ANZCTR


Registration number
ACTRN12617001563358
Ethics application status
Approved
Date submitted
8/11/2017
Date registered
20/11/2017
Date last updated
17/02/2020
Date data sharing statement initially provided
9/01/2019
Date results information initially provided
17/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of intragastric administration of L-tryptophan on appetite and gut hormone release in healthy, normal weight and obese subjects.
Scientific title
Effects of intragastric administration of L-tryptophan on appetite and energy intake, and gut hormone release, in healthy, normal weight and obese subjects.
Secondary ID [1] 293233 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 305270 0
Type 2 Diabetes 305271 0
Healthy Human Gastrointestinal Physiology 305272 0
Condition category
Condition code
Diet and Nutrition 304579 304579 0 0
Obesity
Oral and Gastrointestinal 304580 304580 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 304581 304581 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will receive, in randomized, double-blind fashion, an intragastric bolus infusion (200ml) of i) 3.0g L-tryptophan, ii) 1.5g L-tryptophan, or iii) saline (control), followed 30 min later by an ad libitum buffet style meal. Subjects will receive one infusion per study visit. Study visits will be separated by 3-7 days.

For each study visit, subjects will be asked to attend the clinic at 8:30am (in a fasted state) at which time a baseline 2D ultrasound measurement of their stomach (to obtain antral area for calculation of gastric emptying) will be taken. They will then be provided with a light breakfast (1 piece toast with spread of their choice, 1 cup of tea or water) to consume within 15 minutes . The breakfast provided will be the same at all visits. Water will be provided until 10 am after which time the subject will be asked to take nil by mouth until the lunch meal is provided. Immediately prior to t = -32 (~11:30am), a baseline blood sample, Visual analogue Scale (VAS) questionnaire, and a further ultrasound measurement will be collected. At t = -32 min the infusion will be administered over 2 min using a feeding tube. At t = -20, -10, and 0 min, further blood samples will be collected and VAS completed. At t = -30, -25, -20, -15, -10, -5 and t = 0, ultrasound measurements will be taken. At t = 0 min (~ midday), subjects will be presented with a cold, buffet-style meal. Subjects will be allowed 30 minutes to freely consume food from the buffet meal until comfortably full. At t = 30, 60, 90, 120, and 150 min, further blood samples will be taken and VAS administered.
Intervention code [1] 299491 0
Treatment: Other
Comparator / control treatment
Saline control for within group comparison.
Normal weight control group for between group comparison.
Control group
Placebo

Outcomes
Primary outcome [1] 303799 0
Energy intake at the buffet meal quantified using the computer software program FoodWorks.
Timepoint [1] 303799 0
A buffet meal will be presented during each study visit (t = 0-30). The subject will be allowed to freely consume food until comfortably full for 30 minutes.
Secondary outcome [1] 340198 0
Plasma concentrations of tryptophan and other amino acids, cholecystokinin, and other gastrointestinal hormones (e.g. PYY, ghrelin), This outcome is of an exploratory nature so that other gastrointestinal hormones to be measured may be decided upon based on the effect of the intervention on this and other outcomes.
Timepoint [1] 340198 0
Plasma will be obtained from blood samples taken at t = -32, -20, -10, 0, 30, 60, 90, 120, and 150 min, where t = -32 is just prior to the time of L-tryptophan/saline control administration, and t = 0 is the start of the buffet meal.
Secondary outcome [2] 340199 0
Appetite sensations (hunger, fullness, desire to eat, and amount of food desired to eat) measured using VAS questionnaires.
Timepoint [2] 340199 0
VAS questionnaires will be completed at t = -32, -30, -20, -10, 0, 30, 60, 90, 120, and 150 min min, where t = -32 is just prior to, and t = -30 is immediately after, the time of L-tryptophan/saline control administration, and t = 0 is the start of the buffet meal.
Secondary outcome [3] 340200 0
Size of antral area.
Timepoint [3] 340200 0
2D ultrasound measurements (to obtain antral area) will be taken at t = -32, -30, -25, -20, -15, -10, -5, and 0 min, where t= -32 is just prior to, and t = -30 is immediately after, the time of L-tryptophan/saline control administration, and t = 0 is immediately prior to the start of the buffet meal.

Eligibility
Key inclusion criteria
Healthy lean (BMI 19-25 kg/m2), and healthy obese (BMI 30-37 kg/m2), male subjects aged between 18 - 55 years, non-smoker, and without significant illness will be included in the study.
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Significant gastrointestinal symptoms, disease or surgery;
Current gallbladder or pancreatic disease;
Cardiovascular or respiratory diseases;
Diagnosed type 2 diabetes;
Any other illnesses 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, gastrointestinal function, body weight or appetite (eg domperidone, cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.);
Individuals with low ferritin (less than 30 ug/L) or iron (less than 8 umol/L) levels, or who have donated blood in the 12 weeks prior to taking part in the study;
Lactose intolerance/other food allergy(ies);
Vegetarians;
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;
High performance athletes;
Inability to comprehend study protocol;
Inability to tolerate naso-gastric tube;

Healthy subjects only:
Restrained eaters (score >12 on the three factor eating questionnaire).

Obese subjects only:
HbA1c <6.5%

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 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
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
20/11/2017
Actual
30/11/2017
Date of last participant enrolment
Anticipated
Actual
16/10/2019
Date of last data collection
Anticipated
Actual
30/10/2019
Sample size
Target
20
Accrual to date
Final
25
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 297863 0
Government body
Name [1] 297863 0
National Health and Medical Research Council (NHMRC)
Country [1] 297863 0
Australia
Primary sponsor type
Individual
Name
Prof. Christine Feinle-Bisset
Address
School of Medicine, University of Adelaide
Level 5, Adelaide Health and Medical Sciences Building
Cnr North Terrace and George Street
Adelaide
South Australia 5005
Country
Australia
Secondary sponsor category [1] 296906 0
Individual
Name [1] 296906 0
Michael Horowitz
Address [1] 296906 0
School of Medicine, University of Adelaide
Level 5, Adelaide Health and Medical Sciences Building
Cnr North Terrace and George Street
Adelaide
South Australia 5005
Country [1] 296906 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298912 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 298912 0
Level 3, Roma Mitchell House, North Terrace, Adelaide SA 5000
Ethics committee country [1] 298912 0
Australia
Date submitted for ethics approval [1] 298912 0
27/06/2014
Approval date [1] 298912 0
30/06/2014
Ethics approval number [1] 298912 0
R20140626

Summary
Brief summary
Obesity has reached epidemic proportions globally and is associated with serious co-morbidities, including type 2 diabetes. Once adipose tissue has been accumulated, and food intake is limited by low calorie diets, counter-regulatory mechanisms induce an increase in appetite and a decrease in energy expenditure, which makes weight loss very difficult to maintain. To combat the global burden of obesity and its co-morbidities, a major challenge lies in the development of effective therapies that increase fullness and satiety, and result in improvements in blood glucose control, while lacking adverse effects that are often associated with current therapies.

There is increasing evidence that nutrient stimuli in the gastrointestinal tract play a central role in the control of energy intake and blood glucose. Proteins, and their building blocks, amino acids, are of interest, as high-protein diets are very effective for weight loss, particularly loss of fat, rather than muscle mass, and for improving postprandial glycaemic control, in obese individuals with and without type 2 diabetes. There is some evidence that a number of amino acids (including L-tryptophan) also have effects on energy intake, blood glucose and gut function in humans. We have previously investigated the effects of intraduodenal tryptophan and found that its effects to reduce subsequent energy intake were related to plasma cholecystokinin and tryptophan concentrations prior to the test meal. Thus, amino acids, here specifically tryptophan, may represent potential therapeutic approaches for obesity and type 2 diabetes.

We have recently evaluated the effects of intragastric tryptophan at 3 g on gastric emptying, blood glucose, gut hormones, and appetite following a mixed-nutrient drink. Energy intake at a subsequent buffet style meal was also assessed. L-tryptophan slowed gastric emptying in both lean and obese groups. While overall energy intake was not affected, there was a decrease in energy intake in approximately half the subjects of each group, but less so in the obese. In the lean group, energy intake was found to be related to elevated concentrations of plasma tryptophan. A limitation of this study design may have been too long a duration between tryptophan administration and the meal at which energy intake was assessed (1 hr 15 min), thus mitigating the overall effect on energy intake.

This new study has been designed with a shorter duration between tryptophan administration and buffet meal (30 min) and will investigate the effects of intragastric administration of L-tryptophan, vs saline control, on energy intake at a subsequent ad libitum buffet style meal, and the relationship with plasma gut hormone and tryptophan concentrations, appetite perceptions and intragastric volume in healthy, normal weight and obese, subjects.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78626 0
Prof Christine Feinle-Bisset
Address 78626 0
School of Medicine, University of Adelaide
Level 5, Adelaide Health and Medical Sciences Building
Cnr North Terrace and George Street
Adelaide
South Australia 5005
Country 78626 0
Australia
Phone 78626 0
+61 8 8313 6053
Fax 78626 0
Email 78626 0
[email protected]
Contact person for public queries
Name 78627 0
Prof Christine Feinle-Bisset
Address 78627 0
School of Medicine, University of Adelaide
Level 5, Adelaide Health and Medical Sciences Building
Cnr North Terrace and George Street
Adelaide
South Australia 5005
Country 78627 0
Australia
Phone 78627 0
+61 8 8313 6053
Fax 78627 0
Email 78627 0
[email protected]
Contact person for scientific queries
Name 78628 0
Prof Christine Feinle-Bisset
Address 78628 0
School of Medicine, University of Adelaide
Level 5, Adelaide Health and Medical Sciences Building
Cnr North Terrace and George Street
Adelaide
South Australia 5005
Country 78628 0
Australia
Phone 78628 0
+61 8 8313 6053
Fax 78628 0
Email 78628 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

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Plain language summaryNo Intragastric TRP has a potent energy intake-suppre... [More Details]

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