Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001275954
Ethics application status
Approved
Date submitted
21/10/2020
Date registered
25/11/2020
Date last updated
20/02/2024
Date data sharing statement initially provided
25/11/2020
Date results provided
20/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of amino acids on gut functions in healthy lean individuals
Scientific title
The role of the plasma tryptophan to large neutral amino acid ratio in the effects of amino acids on antropyloroduodenal motility, gut hormone release, appetite and energy intake, cognitive function and mood, in healthy lean individuals
Secondary ID [1] 302526 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 319393 0
Type 2 diabetes 319394 0
Healthy human gastrointestinal physiology 319395 0
Condition category
Condition code
Diet and Nutrition 317359 317359 0 0
Obesity
Oral and Gastrointestinal 317360 317360 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 317361 317361 0 0
Diabetes
Mental Health 317362 317362 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will be studied on four occasions, separated by at least 3 (and up to 7) days. On each occasion, participants will receive, in randomised, double-blind fashion, 90-min intraduodenal infusions of the following treatments: (i) control solution (saline), (ii) L-tryptophan at 0.15 kcal/min (3.3 g over 90 min), (iii) combination of L-tryptophan at 0.15 kcal/min (3.3 g) with L-leucine at 0.22 kcal/min (5 g), or (iv) combination of L-tryptophan at 0.15 kcal/min (3.3 g) with L-leucine at 0.45 kcal/min (10 g). On study days, participants will arrive in the Clinical Research Facility, and will be intubated with a custom-built, soft, silicon manometric catheter (outer diameter: 4 mm; Dentsleeve International, Mui Scientific, Mississauga, Ontario, Canada) that will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. An intravenous cannula will also be placed into a forearm vein for regular blood sampling. Once the catheter has been positioned correctly, fasting motility will be monitored continuously, and immediately after the end of phase III activity of the fasting migrating motor complex, during a period of motor quiescence (i.e. at t = -10 to 0 min), a 10-ml blood sample (baseline) will be taken, and the participant will complete a visual analogue scale questionnaire (VAS) to assess appetite-related perceptions (fullness, hunger, etc.) and GI symptoms (nausea and bloating), the positive and negative affect schedule-short form (PANAS-SF) questionnaire to assess mood, the N-back test and word recall memory test to assess memory, and the Rapid Visual Information Processing (RVIP) test to measure sustained attention. Estimated times required to complete the questionnaires and tests are ~2 min for VAS and PANAS-SF, 2 min for N-back and word recall memory, and 6 min for RVIP. At t = 0 min, the intraduodenal infusion will commence. APD pressures will be measured continually over the 90-min period. Blood samples and VAS ratings will be collected every 15 min from t = 15 to 90 min. PANAS-SF questionnaires will be completed every 30 min from t = 30 to 90 min. The N-back, word recall memory and RVIP tests will be completed at the end of the infusion, from t = 80 min. At t = 90 min, the manometric assembly will be removed and participants will be presented with a cold, buffet-style meal to assess energy intake. The meal consists of 4 slices (~ 120 g) of whole-meal bread, 4 slices (~ 120 g) of white bread, 100 g sliced ham, 100 g sliced chicken, 85 g sliced cheddar cheese, 100 g lettuce, 100 g sliced tomato, 100 g sliced cucumber, 22 g mayonnaise, 20 g margarine, 1 apple (~ 170 g), 1 banana (~ 190 g), 175 g strawberry yogurt, 100 g chocolate custard, 120 g fruit salad, 375 mL iced coffee, 300 mL orange juice, and 600 mL water. Participants will be allowed 30 min to freely consume food until they are comfortably full. The amount of food (g) consumed will be quantified by weighing each food item of the buffet-meal before and after it was presented to the participant. Energy intake (kcal) will be calculated using commercially available software (Foodworks version 8, Xyris Software, Highgate Hill, Queensland, Australia). At t = 120 min (i.e. at the end of the meal) and at t = 180 min, further blood samples will be taken, and questionnaires administered. The intravenous cannula will then be removed and participants will be allowed to leave the laboratory. Participants will be asked to complete a 24-h dietary record (~2 pm to 2 pm) after each visit to monitor their subsequent energy intake.
Intervention code [1] 318814 0
Treatment: Other
Comparator / control treatment
Control solution (0.9% saline)
Control group
Placebo

Outcomes
Primary outcome [1] 325398 0
Energy intake at a buffet meal
Timepoint [1] 325398 0
The amount of energy eaten will be measured from a buffet meal presented between t = 90 - 120 min.
Primary outcome [2] 325399 0
Plasma concentrations of GI hormones (e.g. CCK, PYY, ghrelin and GLP-1, and potentially other, yet to be identified, hormones) and amino acids as composite outcome
Timepoint [2] 325399 0
Plasma will be obtained from blood samples taken at t = -10, 15, 30, 45, 60, 75, 90, 120, 180 min.
Primary outcome [3] 325400 0
Antropyloroduodenal motility will be measured by manometry
Timepoint [3] 325400 0
Motility will be measured continuously between t = -10 - 90 min.
Secondary outcome [1] 387779 0
Appetite perceptions using a VAS questionnaire
Timepoint [1] 387779 0
VAS questionnaires will be completed at t = -10, 15, 30, 45, 60, 75, 90, 120, 180 min.
Secondary outcome [2] 387780 0
Cognitive function including working memory and recall memory as composite outcome
Timepoint [2] 387780 0
N-back test and word recall memory test will be obtained at t = -10, 80, 180 min.
Secondary outcome [3] 387781 0
Cognitive function including attention
Timepoint [3] 387781 0
RVIP test will be obtained at t = -10, 80, 180 min.
Secondary outcome [4] 387782 0
Mood
Timepoint [4] 387782 0
PANAS-SF questionnaires will be obtained at t = -10, 30, 60, 90, 120, 180 min.

Eligibility
Key inclusion criteria
Lean (BMI: 19-25 kg/m2) male participants (aged 18-50 years) who are healthy and do not have chronic illnesses will be included.
Minimum age
18 Years
Maximum age
50 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
- regular GI symptoms, as measured by the GI symptom score (score greater than 1 for any component) or significant GI disease or surgery
- use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, GI function, body weight or appetite (eg domperidone, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.), mood and cognitive function (including benzodiazepines (eg alprazolam), non-benzodiazepine (eg zolpidem), sedatives, antipsychotics (eg aripiprazole), and mood-stabilisers (eg lithium)
- regular medication that may affect any of the study outcomes (i.e. GI motor or hormone functions, appetite or mood) and cannot be discontinued during the study
- lactose intolerance/other food allergy
- current gallbladder or pancreatic disease
- coagulation abnormalities
- oesophageal varices or strictures
- cardiovascular or respiratory diseases that may affect any of the study outcomes and/or tolerance of the naso-duodenal tube
- psychological disorders, anxiety and depression, as assessed by the Kessler Psychological Distress Scale (K10)
- individuals with low serum ferritin levels (less than 30 µg/L), 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 that may affect any of the study outcomes and not explicitly listed above)
- high performance athletes, due to their specific dietary requirements and energy intakes (i.e. much higher than the average population), which affect GI functions and appetite
- current intake of more than 2 standard drinks on more than 5 days per week, due to the known effects of alcohol on GI function, energy intake, mood and cognition
- current smokers/users of tobacco products (including pipe, chewing, cigarettes, cigars, sheesha, vaping etc)
- recreational drug use (e.g marijuana)
- current intake of any illicit substance (since all of these, i.e. tobacco products, marijuana and illicit drugs may affect both GI functions and mood.
- vegetarians
- restrained eaters (score greater than 12 on the 3-factor eating questionnaire)(the degree of eating restraint will be assessed in obese participants, but not used as an exclusion criterion, as obese often have some degree of eating restraint
- diabetes mellitus, as defined by fasting glucose greater than 6.9 mmol/l and/or HbA1c of greater than or equal to 6.5 or less than or equal to 7.9%
- inability to tolerate oro/naso-gastric tube
- inability to comprehend study protocol

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 study 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 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
Pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
8/02/2021
Actual
8/02/2021
Date of last participant enrolment
Anticipated
30/04/2021
Actual
1/12/2022
Date of last data collection
Anticipated
30/05/2021
Actual
1/03/2023
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 306962 0
Government body
Name [1] 306962 0
National Health and Medical Research Council (NHMRC)
Country [1] 306962 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] 307522 0
Individual
Name [1] 307522 0
Prof. Michael Horowitz
Address [1] 307522 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] 307522 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307097 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 307097 0
Ethics committee country [1] 307097 0
Australia
Date submitted for ethics approval [1] 307097 0
05/08/2020
Approval date [1] 307097 0
21/09/2020
Ethics approval number [1] 307097 0
13643

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

Contacts
Principal investigator
Name 106022 0
Prof Christine Feinle-Bisset
Address 106022 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 106022 0
Australia
Phone 106022 0
+61 883136053
Fax 106022 0
Email 106022 0
[email protected]
Contact person for public queries
Name 106023 0
Christine Feinle-Bisset
Address 106023 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 106023 0
Australia
Phone 106023 0
+61 883136053
Fax 106023 0
Email 106023 0
[email protected]
Contact person for scientific queries
Name 106024 0
Christine Feinle-Bisset
Address 106024 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 106024 0
Australia
Phone 106024 0
+61 883136053
Fax 106024 0
Email 106024 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
In line 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.