Clinical trial NCT06942195: Effects of Calcium on Gut Functions and Blood Glucose in Humans With Type 2 Diabetes
Official title: Effects of Intraduodenal Calcium on Plasma Glucose, Glucoregulatory Hormones and Gastric Emptying in Response to a Mixed-nutrient Drink in Humans With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: T2DM
Keywords: intraduodenal
calcium
plasma glucose
Glycaemic control
Glucoregulatory hormones
Gastric emptying
Humans
Lead sponsor: University of Adelaide
Sponsor class: OTHER
First posted: 2025-04-24
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The intervention in this study consists of a 75-min intraduodenal infusion of an isotonic solution containing either calcium chloride (CaCl2) or control (saline).

Participants enrolled into the study will receive, in randomised, double-blind fashion (i) saline (control), (ii) 500 mg CaCl2 or (iii) 1000 mg CaCl2, each occurring on separate sessions. Each study session will be 4-6 hours in duration and will be separated by 3-7 days. Studies will be carried out in the Clinical Research Facility of the Adelaide Medical School, the University of Adelaide, by staff and students trained in the required techniques.

Detailed description: Participants will be required to consume a standardised dinner meal (beef lasagne; total energy content: 602 kcal; McCain Food, Wendouree, Victoria, Australia) the night before each visit by no later than 7 pm. After fasting for \~ 13.5 hours overnight and refraining from exercise and alcohol during the previous 24 hours, participants will arrive in the laboratory at 8.30 am. After confirming adherence to the study requirements, their vital signs, including blood pressure, heart rate and body temperature, will be measured to establish baseline values for safety, and they will be monitored throughout the study. Then, a manometric catheter will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The infusion port will be positioned \~ 14 cm distal to the pylorus. The correct positioning of the catheter will be monitored continuously by measurement of the transmucosal potential difference in the stomach (\~ -40 mV) and the duodenum (\~ 0 mV). Once the catheter has been positioned correctly, an intravenous cannula will be placed into a forearm vein for regular blood sampling. At t = -30 min, a baseline blood sample (7 ml), visual analogue scale (VAS) questionnaire to assess GI symptoms and breath sample to assess gastric emptying will be collected. Then infusion of one of the study treatments (i.e. i) saline, ii) 500 mg CaCl2 or iii) 1000 mg CaCl2) will commence and continue for 75 minutes (t = -30 to t = 45). At t = -1 min, participants will consume, within 1 min, a mixed-nutrient drink (350 mL, containing 500 kcal, 74 g carbohydrates) labelled with 100 mg 13C-acetate for measurement of gastric emptying by non-invasive breath sampling at regular intervals, for subsequent analysis of 13CO2. Blood samples for the measurement of plasma hormone concentrations and glucose, and VAS scores, will be collected before and after the mixed-nutrient drink. At t = 240 min, after collecting final blood and breath samples and VAS scores, the i.v. cannula will be removed and participants will be served a light lunch, after which they will be allowed to leave the laboratory. A total of 98 mL of blood (14 sampling time points, 7 mL each) will be taken on each study day (study total of 310 mL, including screening and glucose tolerance test samples).

Eligibility criteria: Inclusion Criteria:

Males with type 2 diabetes mellitus (T2DM), (BMI: 28-38 kg/m2), will be included in the study. Only men will be included in the study to avoid the confounding effects of the menstrual cycle on gastric emptying. T2DM diagnosis will be based on WHO criteria. HbA1c will be \>=6.5 - \<=7.9% at screening. Blood glucose medications will be required to be withheld for 48 hours prior to each study day. All participants will be required to be weight-stable (i.e. \<5% fluctuation) at study entry, which will be ascertained by a stable body weight in the preceding 4 weeks.

Exclusion Criteria:

* Significant GI symptoms, or history of GI disease or surgery
* Current gallbladder or pancreatic disease
* Cardiovascular or respiratory diseases
* Any other illnesses (except type 2 diabetes) as assessed by the investigator - (including chronic illnesses not explicitly listed above)
* 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)
* Individuals with low ferritin levels (\<30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study
* High performance athletes
* Current intake of \> 2 standard drinks on \> 5 days per week (\>140g/week)
* Current smokers of tobacco (cigarettes, cigars, pipes, sheesha, chewing, vaping etc.)
* Current use of recreational drugs, e.g. marijuana
* Current intake of any illicit substance Vegetarians
* Inability to tolerate nasoduodenal tube
* Inability to comprehend study protocol
* HbA1c \<6% or \>7.9%
* Estimated glomerular filtration rate \<45 ml/min
* Any patient whose medication cannot be withheld for 48 hours for medical reasons

Primary outcomes:
measure: Plasma glucose concentrations
timeFrame: Blood samples will be collected over 4.5 hours: at baseline (time = -30 minutes), then at regular intervals before and after drink administration (times = -25, -15, 0, 10, 20, 30, 45, 60, 75, 90, 120, 180, 240 minutes).
Secondary outcomes:
measure: Gastric emptying
timeFrame: Breath samples will be collected in sealed tubes over 4.5 hours: at baseline (time = -30 minutes) (prior to treatment administration), every 5 minutes after the drink (times = 0 to 60 minutes), then every 10 minutes until 240 minutes post-drink.
measure: Plasma concentrations of glucoregulatory hormones e.g. glucagon-like peptide (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), C-peptide, glucagon, insulin and cholecystokinin (CCK)
timeFrame: Blood samples will be collected over 4.5 hours: at baseline (time = -30 minutes), then at regular intervals before and after the drink (times = -25, -15, 0, 10, 20, 30, 45, 60, 75, 90, 120, 180, 240 minutes).
measure: GI symptoms (nausea and bloating) will be assessed as a composite secondary outcome.
timeFrame: Visual Analogue ratings will be collected over 4.5 hours: at baseline (time = -30 minutes) and at regular intervals before and after the drink (times = -15, 0, 10, 20, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180, 210, 240 minutes).
Other outcomes:
Locations:
city: Adealide
country: Australia
facility: Clinical Research Facility, Adelaide Health and Medical Sciences Building
state: South Australia
Study officials:
affiliation: Adelaide Medical School University of Adelaide Level 5 Adelaide Health and Medical Sciences Building, Cnr George St and North Tce, Adelaide, SA 5005
name: Prof Christine Feinle-Bisset
role: PRINCIPAL_INVESTIGATOR
References: