Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001294943
Ethics application status
Approved
Date submitted
21/10/2020
Date registered
30/11/2020
Date last updated
16/11/2023
Date data sharing statement initially provided
30/11/2020
Date results provided
16/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of calcium and amino acids on gut hormone secretions and bone turnover in healthy males
Scientific title
Effects of intraduodenal calcium and amino acids on the release of gut hormones, upper gastrointestinal motility, energy intake and bone turnover in healthy males
Secondary ID [1] 302159 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy human gastrointestinal physiology 318981 0
Healthy human bone turnover physiology 318982 0
Condition category
Condition code
Diet and Nutrition 316951 316951 0 0
Obesity
Oral and Gastrointestinal 316952 316952 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 316953 316953 0 0
Normal metabolism and endocrine development and function
Musculoskeletal 316954 316954 0 0
Normal musculoskeletal and cartilage development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention in this study consists of a 150 min intraduodenal infusion of a calcium or control solution, combined with L-tryptophan (0.1 kcal/min) from t=75-150 min.

Participants enrolled into the study will receive, in randomized, double-blind fashion
(i) 500 mg CaCl2, combined with L-tryptophan (0.1 kcal/min) from t=75-150 min
(ii) 1000 mg CaCl2, combined with L-tryptophan (0.1 kcal/min) from t=75-150 min
(iii) Saline (control), combined with L-tryptophan (0.1 kcal/min) from t=75-150 min

each occurring at separate visits. Each visit will last 4.5-6 hrs in duration and will be separated by 3-7 days. Visits will be carried out in the Clinical Research Facility of the Discipline of Medicine, the University of Adelaide by staff members trained in the required techniques, and will be conducted on an individual basis.

Participants will be asked to consume a standardised dinner meal (Beef lasagne; total energy content: 602kcal; McCain Food, Wendouree, Victoria, Australia) the night before each visit by no later than 6 pm, After fasting for 14 hrs overnight and refraining from exercise and alcohol for 24 hrs, participants will arrive at the laboratory at 8 am. Upon arrival, participants 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 forearm vein for regular blood sampling to measure blood glucose, plasma hormone (e.g. gastrin, CCK, GIP, GLP-1, and potentially other, including yet to be identified, gut hormones) and bone marker (CTX, PTH) concentrations. 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 (i.e. at t = -15 to -1 min), two 9-mL venous blood samples (baseline) will be taken (at t = -15 and -5 min), 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). At t = 0 min (during phase I of the MMC), one of three infusions (i) saline or ii) calcium (500 mg) or iii) calcium (1000mg) will commence. At t = 75 min an intraduodenal infusion of L-tryptophan (same rate on all three study days) will be added for 75 mins.

Antropyloroduodenal (APD) pressures will be measured continually for 150 min (t = 0-150 min). Vital signs (blood pressure, heart rate) will be measured at regular time intervals using a commercially available sphygmomanometer/blood pressure meter. At t = 150 min, the manometric assembly will be removed and participants will be presented with a standardised cold, buffet-style meal, which is used to assess energy intake. Participants will be allowed 30 min to freely consume food until they are comfortably full. At t = 180 min, a final blood sample and VAS questionnaire will be collected. The intravenous cannula will then be removed and participants will be allowed to leave the laboratory. A total of 135 mL of blood will be taken on each study day (study total of 413 mL, including screening test).
Intervention code [1] 318546 0
Treatment: Other
Comparator / control treatment
Saline
Control group
Placebo

Outcomes
Primary outcome [1] 325053 0
Plasma concentrations of GI hormones (gastrin, CCK, GIP, GLP-1, and potentially other, including yet to be identified, gut hormones), and glucose.
This outcome is of an exploratory nature so that specific hormones to be measured may be decided upon based on the effect of the intervention on this and other outcomes, therefore, this is a composite outcome.
Timepoint [1] 325053 0
These will be assessed from venous blood samples taken before infusion ( t = -15, -5) and during study at regular time points for 3 hours (t= 5, 15, 30, 45, 60, 75, 80, 90, 105, 120, 135, 150, 180 min)
Primary outcome [2] 325054 0
Markers of bone remodelling and calcium homeostasis (CTX, PTH)
Timepoint [2] 325054 0
These will be assessed from venous blood samples taken before infusion ( t = -15, -5) and during study at regular time points for 3 hours (t= 5, 15, 30, 45, 60, 75, 80, 90, 105, 120, 135, 150, 180 min)
Secondary outcome [1] 386680 0
Antropyloroduodenal (APD) pressures.
Timepoint [1] 386680 0
This will be measured continually for 150 min (t = 0-150 min) using the manometric catheter, measuring pressures in the antrum, pylorus, and duodenum.
Secondary outcome [2] 386681 0
Appetite ratings (hunger, fullness, desire to eat, and prospective consumption), and GI symptoms (nausea and bloating).
This outcome is of an exploratory nature so that specific parameters to be measured may be decided upon based on the effect of the intervention on this and other outcomes, therefore, this is a composite outcome.
Timepoint [2] 386681 0
This will be measured using a 100mm Visual Analogue Scale (VAS). This VAS has been extensively employed in published studies conducted by the investigators.
VAS will be collected before infusion (t= -15) and during study at regular time points for 3 hours (t= 0,15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180)
Secondary outcome [3] 386682 0
Energy intake at a buffet lunch.
Timepoint [3] 386682 0
At t=150, participants will be presented with a standardised cold, buffet-style meal, which is used to assess energy intake. The meal comprises 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. The meal has a total energy content of ~2300 kcal (~27% fat, ~52% carbohydrate, and ~21% protein)and weight of ~2924 g. Participants will be allowed 30 min to freely consume food until they are comfortably full. Each food item will be weighed before and after being offered to the participants and energy intake and macronutrient composition calculated using commercially available software (Foodworks 8.0, Xyris Software, Highgate Hill, QLD, Australia).

Eligibility
Key inclusion criteria
Healthy
Lean weight (BMI 19-25 kg/m2)
Minimum age
18 Years
Maximum age
50 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Each participant will be questioned prior to the study to exclude:
- significant GI symptoms, 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 (e.g. domperidone, cisapride, anticholinergic drugs (e.g. 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
- individuals with low ferritin levels (females <15 ng/mL, males <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 > 2 standard drinks on > 5 days per week
- current smokers of tobacco (cigarettes, cigars, pipes, sheesha, chewing, vaping etc.)
- recreational drug use, e.g marijuana
- current intake of any illicit substance
- vegetarians
- inability to tolerate nasoduodenal tube
- inability to comprehend study protocol
- restrained eaters (score >12 on the 3-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)
Eligible volunteers are assigned a participant number and randomised treatment for each study visit. Randomisation involves contacting the holder (study assistant) of the randomisation table to inform them of participant details and study dates. The unblinded study assistant is, therefore, responsible for allocating a random treatment to the participant and administering the dose.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation is generated using a randomisation 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
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/01/2021
Actual
20/01/2021
Date of last participant enrolment
Anticipated
31/03/2022
Actual
24/03/2022
Date of last data collection
Anticipated
20/04/2022
Actual
20/04/2022
Sample size
Target
15
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 306587 0
Government body
Name [1] 306587 0
NHMRC
Country [1] 306587 0
Australia
Primary sponsor type
Individual
Name
Christine Feinle-Bisset
Address
Adelaide Medical School
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] 307115 0
Individual
Name [1] 307115 0
Michael Horowitz
Address [1] 307115 0
Adelaide Medical School
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce,
Adelaide, SA 5005
Country [1] 307115 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306769 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 306769 0
Ethics committee country [1] 306769 0
Australia
Date submitted for ethics approval [1] 306769 0
20/05/2020
Approval date [1] 306769 0
29/07/2020
Ethics approval number [1] 306769 0
13243

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

Contacts
Principal investigator
Name 104962 0
Prof Christine Feinle-Bisset
Address 104962 0
Adelaide Medical School University of Adelaide Level 5 Adelaide Health and Medical Sciences Building, Cnr George St and North Tce, Adelaide, SA 5005
Country 104962 0
Australia
Phone 104962 0
+61 8 8313 6053
Fax 104962 0
Email 104962 0
[email protected]
Contact person for public queries
Name 104963 0
Christine Feinle-Bisset
Address 104963 0
Adelaide Medical School University of Adelaide Level 5 Adelaide Health and Medical Sciences Building, Cnr George St and North Tce, Adelaide, SA 5005
Country 104963 0
Australia
Phone 104963 0
+61 8 8313 6053
Fax 104963 0
Email 104963 0
[email protected]
Contact person for scientific queries
Name 104964 0
Christine Feinle-Bisset
Address 104964 0
Adelaide Medical School University of Adelaide Level 5 Adelaide Health and Medical Sciences Building, Cnr George St and North Tce, Adelaide, SA 5005
Country 104964 0
Australia
Phone 104964 0
+61 8 8313 6053
Fax 104964 0
Email 104964 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


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.