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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 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]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Obesity

Type 2 Diabetes

Healthy Human Gastrointestinal Physiology

Condition category

Condition code

Diet and Nutrition

Obesity

Oral and Gastrointestinal

Normal oral and gastrointestinal development and function

Metabolic and Endocrine

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]

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]

Energy intake at the buffet meal quantified using the computer software program FoodWorks.

Timepoint [1]

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]

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]

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]

Appetite sensations (hunger, fullness, desire to eat, and amount of food desired to eat) measured using VAS questionnaires.

Timepoint [2]

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]

Size of antral area.

Timepoint [3]

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council (NHMRC)

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra
ACT 2601

Country [1]

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]

Individual

Name [1]

Michael Horowitz

Address [1]

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]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Central Adelaide Local Health Network Human Research Ethics Committee

Ethics committee address [1]

Level 3, Roma Mitchell House, North Terrace, Adelaide SA 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

27/06/2014

Approval date [1]

30/06/2014

Ethics approval number [1]

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

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

Phone

+61 8 8313 6053

Fax

christine.feinle@adelaide.edu.au

Contact person for public queries

Name

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

Phone

+61 8 8313 6053

Fax

christine.feinle@adelaide.edu.au

Contact person for scientific queries

Name

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

Phone

+61 8 8313 6053

Fax

christine.feinle@adelaide.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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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Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Plain language summary	No		Intragastric TRP has a potent energy intake-suppre... [More Details]

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