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Trial registered on ANZCTR


Registration number
ACTRN12616001595404
Ethics application status
Approved
Date submitted
10/11/2016
Date registered
18/11/2016
Date last updated
14/04/2020
Date data sharing statement initially provided
9/11/2018
Date results information initially provided
14/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of intragastric administration of L-phenylalanine on gastric emptying, gut hormone release, blood glucose and energy intake in healthy, normal weight subjects.
Scientific title
Effects of intragastric administration of L-phenylalanine on gastric emptying, gut hormone release, blood glucose and energy intake in healthy, normal weight subjects.
Secondary ID [1] 290410 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 300749 0
Type 2 diabetes 300750 0
Healthy human gastrointestinal physiology 300751 0
Condition category
Condition code
Diet and Nutrition 300583 300583 0 0
Obesity
Oral and Gastrointestinal 300584 300584 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 300585 300585 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial is comprised of two study parts:
Part A: Assessment of energy intake,
Part B: Assessment of blood glucose and gastric emptying,
following administration of 0g, 5g, or 10g L-phenyalalanine 30 min prior to a meal (Part A: ad libitum buffet style meal; Part B: standardised Ensure drink meal).
Although it will not be required, subjects will be invited to participate in both parts.

In each of Parts A and B, subjects will receive, in randomized, double-blind fashion, an intragastric bolus infusion (100ml) of i) 5g L-phenylalanine; ii) 10g L-phenylalanine; iii) saline (control). Subjects will receive one infusion per visit. Study visits will be separated by 3-7 days.

Part A:
For each study visit a baseline blood sample, and Visual analogue Scale (VAS) questionnaire will be collected (t = -31) . At t = -31 min the infusion will be administered over 1 minute using a feeding tube. At t = -20, -10, and 0 min, a further blood sample will be collected and VAS completed. At t = 0 min, subjects will be presented with a cold, buffet-style meal. Subjects will be allowed 30 minutes to freely consume the buffet meal until comfortably full. At t = 30, and 60 min further blood samples will be taken, and VAS administered,

Part B:
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 (Ensure, 400 kcal, 300 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] 296271 0
Treatment: Other
Comparator / control treatment
Saline control for within group comparison.
Healthy control group for between group comparison.
Control group
Placebo

Outcomes
Primary outcome [1] 300073 0
Part A:
Energy intake at the buffet meal measured using the computer software program FoodWorks.

Timepoint [1] 300073 0
Part A:
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.


Primary outcome [2] 300235 0
Part B:
Blood glucose before and after infusion administration, and following the mixed nutrient Ensure drink.
Timepoint [2] 300235 0
Part B:
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-phenylalanine administration and t = -1 is just prior to nutrient drink consumption.
Secondary outcome [1] 329187 0
Part A:
Plasma concentrations of gastrointestinal hormones (e.g. CCK, PYY, and ghrelin),

Timepoint [1] 329187 0
Part A:
Gut hormone release will be assessed from blood samples taken at t = -31, -20, -10, 0, 30, 60 min, where t = -31 is just prior to the time of L-phenylalanine administration and t = 0 is the start of the buffet meal.

Secondary outcome [2] 329441 0
Part B:
Gastric Emptying (measurement of 13CO2 in breath samples); Plasma concentrations of gastrointestinal hormones (e.g. GLP-1, GIP ), insulin, glucose and 3-OMG.
Timepoint [2] 329441 0
Part B:
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; Gut hormone release will be assessed from blood samples taken at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min, where t = -31 is just prior to the time of L-phenylalanine administration and t = -1 is just prior to nutrient drink consumption.
Secondary outcome [3] 329442 0
Parts A and B:
Appetite sensations using a VAS questionnaire (satiety, hunger, fullness, desire to eat, and amount of food desired to eat).
Timepoint [3] 329442 0
Part A:
VAS questionnaires will be completed at t = -31, -20, -10, 0, 30, and 60 min, where t = -31 is just prior to the time of L-phenylalanine administration and t = 0 is the start of the buffet meal.

Part B:
VAS questionnaires will be completed at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min, where t = -31 is just prior to the time of L-phenylalanine administration and t = -1 is just prior to nutrient drink consumption.

Eligibility
Key inclusion criteria
A total of 16 healthy, lean (BMI 19-25 kg/m2) male subjects, aged between 18 - 55 years, will be included in each study part.
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Significant gastrointestinal symptoms, disease or surgery;
Current gallbladder or pancreatic disease;
Cardiovascular or respiratory diseases;
Phenylketonuria; .
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 and cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.);
Individuals 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;
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;
Restrained eaters (score >12 on the three factor eating questionnaire);
Inability to comprehend study protocol;
Unable to tolerate naso-gastric tube.

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 allocationg 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
Data relating to gastric emptying, intestinal glucose absorption, glucose and hormone concentrations and appetite profiles will be analysed using repeated-measures analysis of variance (ANOVA), with time and treatment as factors. One-way ANOVA will be used to evaluate AUC data for appetite and gut hormones, and total macronutrient and energy intake from the buffet meal. Relationships between the outcomes will be evaluated using regression analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 294888 0
Government body
Name [1] 294888 0
NHMRC
Address [1] 294888 0
National Health and Medical Research Council
GPO Box 1421
Canberra
ACT 2601
Country [1] 294888 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] 293725 0
Individual
Name [1] 293725 0
Michael Horowitz
Address [1] 293725 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] 293725 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296267 0
Central Adelaide Local Health Network Research Ethics Committee
Ethics committee address [1] 296267 0
Level 3, Roma Mitchell House,
North Terrace
Adelaide SA 5000
Ethics committee country [1] 296267 0
Australia
Date submitted for ethics approval [1] 296267 0
Approval date [1] 296267 0
30/06/2014
Ethics approval number [1] 296267 0
140626

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 good 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, since 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-phenylalanine) may also have effects on energy intake, blood glucose and gut function in humans. Thus, they are of special interest in terms of potential therapeutic approaches for obesity and type 2 diabetes.

This is an exploratory study and will investigate the dose-related effects of intragastric administration of L-phenylalanine on gastric emptying, gut hormone release, glycaemic control, appetite perceptions and energy intake in healthy, normal weight subjects.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 70002 0
Prof Christine Feinle-Bisset
Address 70002 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 70002 0
Australia
Phone 70002 0
+61 8 8313 6053
Fax 70002 0
Email 70002 0
christine.feinle@adelaide.edu.au
Contact person for public queries
Name 70003 0
Prof Christine Feinle-Bisset
Address 70003 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 70003 0
Australia
Phone 70003 0
+61 8 8313 6053
Fax 70003 0
Email 70003 0
christine.feinle@adelaide.edu.au
Contact person for scientific queries
Name 70004 0
Prof Christine Feinle-Bisset
Address 70004 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 70004 0
Australia
Phone 70004 0
+61 8 8313 6053
Fax 70004 0
Email 70004 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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary