Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000715370
Ethics application status
Approved
Date submitted
4/05/2017
Date registered
17/05/2017
Date last updated
18/03/2019
Date data sharing statement initially provided
18/03/2019
Date results provided
18/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of small intestinal L-valine on gut function, gut hormone release and blood glucose control in healthy, lean volunteers.
Scientific title
Effects of intraduodenal L-valine on antropyloroduodenal motility, gut hormone release, blood glucose control and energy intake in healthy, lean volunteers.
Secondary ID [1] 291790 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 303022 0
Type 2 Diabetes 303023 0
Healthy Human Gastrointestinal Physiology 303024 0
Condition category
Condition code
Diet and Nutrition 302481 302481 0 0
Obesity
Oral and Gastrointestinal 302482 302482 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 302483 302483 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention in this study consists of the intraduodenal infusion of an L-valine or control solution over a 90 minute period during which the measurement of gut motility, blood glucose, gut hormone concentration, insulin concentrations, appetite perceptions and energy intake during a buffet meal will be measured.

Subjects enrolled into the study will receive, in randomized, double-blind fashion
(i) 0.15 kcal/min L-valine,
(ii) 0.45 kcal/min L-valine,
(iii) saline (control),
each occurring at separate visits. Each visit will last 3-6hrs in duration, and will be separated by 3-7 days. Visits will be carried out in the clinic room facility of the Discipline of Medicine, University of Adelaide by staff members trained in the required techniques, and will be conducted on an individual basis.

Subjects will be asked to consume a standardised dinner meal the night before each visit by no later than 6pm, After fasting for 14 hrs overnight and refraining from exercise and alcohol for 24 hrs, subjects will arrive at the laboratory at 8am . Upon arrival, subjects will be intubated with a 17-channel manometric catheter that will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The manometric catheter consists of 16 side holes spaced at 1.5 cm intervals, measuring pressures in the antrum, pylorus, and duodenum (APD pressures). An additional channel (with the side hole positioned approx 14 cm distal to the pylorus when the catheter is in position) is used for intraduodenal infusions. The correct positioning of the catheter will be maintained by continuous measurement of the transmucosal potential difference (TMPD) between the most distal antral channel and the most proximal duodenal channel. All manometric channels will be perfused with degassed, distilled water, except for the two TMPD channels, which will be perfused with degassed 0.9% saline, at 0.15 ml/min. An intravenous cannula will be placed into a right forearm vein for regular blood sampling to measure plasma hormone concentrations and blood glucose. 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 (MMC), during a period of motor quiescence (t=-15 - 0 min), a 12 ml venous blood sample (baseline) will be taken, and the subject will complete a visual analogue scale questionnaire (VAS) to assess appetite-related perceptions (fullness, hunger, etc.) and gastrointestinal symptoms (nausea and bloating). At t = 0 min (during phase I of the MMC), the 90-min intraduodenal infusion (either (i), (ii), or (iii) as outlined above) will commence . APD pressures will be measured continually over the 90-min period. Blood samples will be collected and VASs completed every 15 min from t = 0 to 90 min. At t = 90 min, the manometric catheter will be removed and subjects will be presented with a cold, buffet-style meal. Subjects will be allowed 30 min to freely consume food until they are comfortably full. At t = 120 min, a final blood sample will be taken, and VAS administered. The intravenous cannula will then be removed and subjects will be allowed to leave the laboratory. A total of 96 ml of blood will be taken on each study day (288 ml over all study visits).
Intervention code [1] 297903 0
Treatment: Other
Comparator / control treatment
Saline
Control group
Placebo

Outcomes
Primary outcome [1] 301897 0
Energy intake at the buffet meal. The weight of the foods will be recorded before and after being offered to the subjects and energy intake and macronutrient composition calculated subsequently using commercially available software (Foodworks, Xyris Software, Highgate Hill, QLD, Australia).
Timepoint [1] 301897 0
A buffet meal will be presented immediately following each intraduodenal infusion (t = 90 - 120 min). The subject will be allowed to freely consume food until comfortably full for 30 minutes.
Primary outcome [2] 301898 0
Antropyloroduodenal motility (number of antral, duodenal and isolated pyloric pressure waves, and basal pyloric pressure) will be measured using a 17-channel manometric assembly (Dentsleeve, Mui Scientific).
Timepoint [2] 301898 0
Baseline (t = -15 - 0 min) and during intraduodenal infusion (t = 0 - 90 min).
Primary outcome [3] 301899 0
Plasma concentrations of gastrointestinal hormones (e.g. CCK, GLP-1, PYY, GIP and ghrelin), insulin and glucose will be assessed by Enzyme-linked Immunosorbent Assay (ELISA) or Radio Immnunosorbent Assay (RIA).

This intervention is of an exploratory nature to characterise the effects of varying doses of L-valine. As such, it is unknown which plasma hormone concentrations may prove to be of importance. Hence these have been grouped into one composite primary outcome.
Timepoint [3] 301899 0
15 minute intervals from t=-15 - 90 min, and 120 min.
Secondary outcome [1] 334242 0
Appetite sensations (hunger, fullness, thirst, desire to eat, amount of food the subject thinks they could eat) and gastrointestinal symptoms (nausea, bloating) will be measured using a 100mm Visual Analogue Scale (VAS). This VAS has been extensively employed in published studies conducted by the investigators.

This intervention is of an exploratory nature to characterise the effects of varying doses of L-valine. As such, it is unknown which appetite sensations or gastrointestinal symptoms may prove to be of importance. Hence these have been grouped into one composite secondary outcome.
Timepoint [1] 334242 0
15 minute intervals from t=-15 - 90 min, and 120 min.
Secondary outcome [2] 334427 0
Blood glucose will be assessed using a portable glucometer (Freestyle Optium H, Abbott Diabetes Care Ltd, VIC, Australia) .
Timepoint [2] 334427 0
15 minute intervals from t=-15 - 90 min, and 120 min.

Eligibility
Key inclusion criteria
A total of 12 healthy, lean (BMI 19-25 kg/m2) male subjects, aged between 18 - 55 years will be included. 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 preceding 4 weeks.
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
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)

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)
Allocation involves contacting the holder of the randomisation table (study assistant) to inform them of the next subjects details and study dates. The unblinded study assistant is therefore responsible for allocating a randomly generated treatment sequence to the subject and preparing the intraduodenal infusion 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
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/05/2017
Actual
4/08/2017
Date of last participant enrolment
Anticipated
Actual
31/05/2018
Date of last data collection
Anticipated
Actual
15/06/2018
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 296294 0
Government body
Name [1] 296294 0
National Health and Medical Research Council (NHMRC)
Country [1] 296294 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 Street and North Tce
Adelaide, SA 5005
Country
Australia
Secondary sponsor category [1] 295217 0
Individual
Name [1] 295217 0
Michael Horowitz
Address [1] 295217 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building
Cnr George Street and North Tce
Adelaide, SA 5005
Country [1] 295217 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297525 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 297525 0
Ethics committee country [1] 297525 0
Australia
Date submitted for ethics approval [1] 297525 0
27/06/2013
Approval date [1] 297525 0
28/06/2013
Ethics approval number [1] 297525 0
RAH Protocol No: R20130611 HREC/13/RAH/245

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

Contacts
Principal investigator
Name 74326 0
Prof Christine Feinle-Bisset
Address 74326 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building
Cnr George Street and North Tce
Adelaide, SA 5005
Country 74326 0
Australia
Phone 74326 0
+61 8 8313 6053
Fax 74326 0
Email 74326 0
[email protected]
Contact person for public queries
Name 74327 0
Christine Feinle-Bisset
Address 74327 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building
Cnr George Street and North Tce
Adelaide, SA 5005
Country 74327 0
Australia
Phone 74327 0
+61 8 8313 6053
Fax 74327 0
Email 74327 0
[email protected]
Contact person for scientific queries
Name 74328 0
Christine Feinle-Bisset
Address 74328 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building
Cnr George Street and North Tce
Adelaide, SA 5005
Country 74328 0
Australia
Phone 74328 0
+61 8 8313 6053
Fax 74328 0
Email 74328 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
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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseIntraduodenal administration of L-valine has no effect on antropyloroduodenal pressures, plasma cholecystokinin concentrations or energy intake in healthy, lean men.2019https://dx.doi.org/10.3390/nu11010099
N.B. These documents automatically identified may not have been verified by the study sponsor.