Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000739718
Ethics application status
Approved
Date submitted
3/05/2022
Date registered
23/05/2022
Date last updated
10/05/2024
Date data sharing statement initially provided
23/05/2022
Date results provided
10/05/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of calcium and amino acids on gut hormone secretions and bone turnover in males with obesity (with or without impaired glucose tolerance or type 2 diabetes)
Scientific title
Effects of intraduodenal calcium and amino acids on the release of gut hormones, upper gastrointestinal motility, energy intake and bone turnover markers in males with obesity (with or without impaired glucose tolerance or type 2 diabetes)
Secondary ID [1] 307005 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
obesity 326123 0
Impaired bone turnover physiology 326124 0
Impaired glucose tolerance 326259 0
Type 2 diabetes 326260 0
Condition category
Condition code
Diet and Nutrition 323446 323446 0 0
Obesity
Musculoskeletal 323447 323447 0 0
Other muscular and skeletal disorders
Metabolic and Endocrine 323448 323448 0 0
Other endocrine disorders
Metabolic and Endocrine 323449 323449 0 0
Diabetes

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 solution, combined with L-tryptophan (0.1 kcal/min) from t=75-150 min.

Participants enrolled into the study will receive, in a 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

each occurring at separate visits. The total duration of each study visit will be 4.5-6 hours. Study visits will be separated by 3-7 days and will be performed in the Clinical Research Facility of the Adelaide Medical School, University of Adelaide by staff and students trained in the required techniques.

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 7 pm. After being fasted for 14 hrs overnight and refraining from any exercise and alcohol intake 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 and an additional channel (with the side hole positioned approx. 14 cm distal to the pylorus when the catheter is in the correct 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. 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 0 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). At t = 0 min (during phase I of the MMC), one of the infusions (i) calcium (500 mg) or ii) calcium (1000mg) will commence. At t = 75 min an intraduodenal infusion of L-tryptophan (same rate on all study days) will be added for 75 min.

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 (containing ~2300 kcal, ~27% fat, ~52% carbohydrate, and ~21% protein) and will be allowed 30 min to freely consume food until they are comfortably full. At t = 180 min, the intravenous cannula will be also 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 417mL, including screening test).
Intervention code [1] 323451 0
Treatment: Other
Comparator / control treatment
On the control days, participants will receive, in a randomized, double-blind fashion, a 150 min infusion of saline (sodium chloride 0.9%), which will be combined with an infusion of L-tryptophan (0.1 kcal/min) from t=75-150 min.
Control group
Active

Outcomes
Primary outcome [1] 331183 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] 331183 0
These will be assessed before infusion (t = -15, -5 min) and post-infusion commencement 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] 331184 0
Plasma markers of bone remodelling and calcium homeostasis (CTX, PTH)
Timepoint [2] 331184 0
These will be assessed before infusion (t = -15, -5 min) and post-infusion commencement 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] 409107 0
Antropyloroduodenal (APD) pressures will be assessed using the manometric catheter, measuring pressures in the antrum, pylorus, and duodenum.
Timepoint [1] 409107 0
This will be measured continually for 150 min post-infusion commencement (t = 0-150 min).
Secondary outcome [2] 409108 0
Appetite ratings (hunger, fullness, desire to eat, and prospective consumption), and GI symptoms (nausea and bloating) will be assessed using a 100mm visual analogue scale (VAS) questionnaire. This VAS has been extensively employed in published studies conducted by the investigators. 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] 409108 0
These will be collected before infusion (t= 0 min) and post-infusion commencement at regular time points for 3 hours (t= 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180 min) .
Secondary outcome [3] 409109 0
Energy intake will be measured using a standardised cold, buffet-style meal. The meal has a total energy content of ~2300 kcal (~27% fat, ~52% carbohydrate, and ~21% protein), a weight of ~2924 g and 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. Each food item will be weighed before and after being offered to the participants, who will be allowed to freely consume food until they are comfortably full. Energy intake and macronutrient composition calculated using commercially available software (Foodworks 8.0, Xyris Software, Highgate Hill, QLD, Australia).
Timepoint [3] 409109 0
This will be assessed 30 minutes after offering the standardised meal to the participants (i.e. at 180 min post-infusion commencement).
Secondary outcome [4] 409536 0
Vital signs (blood pressure, heart rate) will be measured using a commercially available sphygmomanometer/blood pressure meter.
Timepoint [4] 409536 0
These will be collected before infusion (t= 0 min) and post-infusion commencement at regular time points for 3 hours (t= 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180 min) .

Eligibility
Key inclusion criteria
15 male individuals (aged 18-70 yrs) with obesity (BMI: 28-38 kg/m2, waist circumference >= 102 cm), with or without impaired glucose tolerance (IGT), including type 2 diabetes (T2D), at screening, will be studied. At screening, HbA1c will be in the range of >=6% to <=7.9% and fasting blood glucose in the range of >=6.1 mmol/L to <7 mmol/L will be classified as IGT and fasting blood glucose >=7 mmol/L will be classified as type 2 diabetes. Blood glucose medications will be withheld for 48 hours prior to each study day. Participants will be required to be weight-stable (i.e. <5% fluctuation) at study entry; this will be ascertained by asking participants about any significant body weight change in the preceding 3 months and, if so, those individuals would be excluded.
Minimum age
18 Years
Maximum age
70 Years
Sex
Males
Can healthy volunteers participate?
No
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, bodyweight 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 (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)
- HbA1c <6% or >7.9%
- any patient whose medication cannot be withheld for 48 hours for medical reasons;
- estimated glomerular filtration rate <45 ml/min
- autonomic nerve function damage, i.e. a score of =>3 from standardised cardiovascular reflex tests.

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 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
25/05/2022
Actual
19/05/2022
Date of last participant enrolment
Anticipated
6/05/2023
Actual
31/03/2023
Date of last data collection
Anticipated
30/05/2023
Actual
28/04/2023
Sample size
Target
15
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 311316 0
Government body
Name [1] 311316 0
National Health and Medical Research Council (NHMRC)
Country [1] 311316 0
Australia
Funding source category [2] 311354 0
Charities/Societies/Foundations
Name [2] 311354 0
Diabetes Australia
Country [2] 311354 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] 312687 0
Individual
Name [1] 312687 0
Michael Horowitz
Address [1] 312687 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] 312687 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310819 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 310819 0
Ethics committee country [1] 310819 0
Australia
Date submitted for ethics approval [1] 310819 0
30/03/2022
Approval date [1] 310819 0
20/04/2022
Ethics approval number [1] 310819 0

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

Contacts
Principal investigator
Name 118974 0
Prof Christine Feinle-Bisset
Address 118974 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 118974 0
Australia
Phone 118974 0
+61 8 8313 6053
Fax 118974 0
Email 118974 0
[email protected]
Contact person for public queries
Name 118975 0
Christine Feinle-Bisset
Address 118975 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 118975 0
Australia
Phone 118975 0
+61 8 8313 6053
Fax 118975 0
Email 118975 0
[email protected]
Contact person for scientific queries
Name 118976 0
Christine Feinle-Bisset
Address 118976 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 118976 0
Australia
Phone 118976 0
+61 8 8313 6053
Fax 118976 0
Email 118976 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.