None listed
Conditions
Brief summary
The purpose of this trial is to investigate the effects of calcium alone and in combination with the amino acid, L-tryptophan, on gastrointestinal functions, associated with the regulation of appetite and energy intake in males with obesity (with or without impaired glucose tolerance or type 2 diabetes).
Interventions
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 hou
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).
Sponsors
Christine Feinle-Bisset
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
Male
Age
18 Years to 70 Years
Healthy volunteers
No
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.
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.
Outcome results
None listed