Effects of Calcium on Gut Functions and Blood Glucose in Humans With Type 2 Diabetes

University of Adelaide

Status: Begins enrollment this month

Conditions: T2DM

Treatments: Other: Ca-500; Other: Ca-1000; Other: Control

Study type: Interventional

Funder types: Other

Identifiers

NCT06942195

13243-1

Details and patient eligibility

About

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.

Full 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).

Enrollment: 15 estimated patients

Sex: Male

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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15 participants in 3 patient groups, including a placebo group

Ca-1000

Active Comparator group

Description:

In this arm, participants will receive a 75-minute intraduodenal infusion of an isotonic solution containing 3.68 g of calcium chloride dihydrate (CaCl₂·2H₂O), dissolved in 225 mL of distilled water.

Treatment:

Other: Ca-1000

Ca-500

Active Comparator group

Description:

In this arm, participants will receive a 75-minute intraduodenal infusion of an isotonic solution containing 1.84 g of calcium chloride dihydrate (CaCl₂·2H₂O), dissolved in 225 mL of distilled water. Additionally, 1.2 g of sodium chloride (NaCl) will be added to ensure the solution is isosmotic (300 mOsm).

Treatment:

Other: Ca-500

Control

Placebo Comparator group

Description:

In this arm, participants will receive a 75-minute intraduodenal infusion of saline (an isotonic solution containing 2.8 g of sodium chloride (NaCl), dissolved in 225 mL of distilled water).

Treatment:

Other: Control