Clinical trial NCT02324010: Effects of Sitagliptin on Gastric Emptying, Glycaemia and Blood Pressure in Type 2 Diabetes
Official title: Effects of Sitagliptin on Postprandial Glycaemia, Incretin Hormones and Blood Pressure in Type 2 Diabetes - Relationship to Gastric Emptying
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroparesis
Diabetes Mellitus
Keywords: gastric emptying
glycemia
appetite
incretin hormones
Lead sponsor: Royal Adelaide Hospital
Sponsor class: OTHER
First posted: 2014-12-24
Enrollment: 14
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the acute effects of sitagliptin on postprandial glycemia, incretin hormones and blood pressure, and the relationship to gastric emptying, after a mashed potato meal in patients with type 2 diabetes.

Detailed description: The purpose of this study is to (i) evaluate the acute effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin (100mg once daily for two days), on gastric emptying, postprandial plasma glucose, insulin, glucagon and 'incretin' hormones (ie. glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)), blood pressure and heart rate after a high carbohydrate meal, and (ii) to determine whether the magnitude of the effects of sitagliptin on postprandial glycaemia and blood pressure is related to the rate of gastric emptying, in patients with type 2 diabetes.

The rate of entry of carbohydrate into the small intestine is especially important in patients with diabetes mellitus. Sitagliptin is an orally administered inhibitor of dipeptidyl-peptidase-IV (DPP-IV), the enzyme responsible for the degradation of GLP-1. It is hypothesized that sitagliptin will increase the GLP-1 response to, and thereby slow gastric emptying and diminish the glycaemic and blood pressure response to, a carbohydrate-containing meal.

Twenty healthy subjects (male and female) will be studied. Each subject will be studied on two occasions following treatment for 2 days with sitagliptin (100mg once daily) or matching placebo in a randomized, double blind, crossover design. Measurements of gastric emptying, intragastric meal distribution, blood glucose concentrations, gut hormones, blood pressure, splanchnic flow and appetite will be measured for 4 hours following ingestion of a mashed potato meal.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet or metformin alone
* Body mass index (BMI) 20 - 40 kg/m2
* Males and females (females of reproductive potential must be using an appropriate contraceptive method)
* Glycated haemoglobin (HbA1c) ≤ 8.5%
* Haemoglobin above the lower limit of the normal range (i.e. \>135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (i.e. \>10mcg/L)

Exclusion Criteria:

* Subjects with gastrointestinal disease, significant upper or lower gastrointestinal symptoms, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy)
* Other significant illness, including epilepsy, cardiovascular or respiratory disease.
* History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy.
* Impaired renal or liver function (as assessed by calculated creatinine clearance \< 50 mL/min using the Cockroft-Gault equation (27) or abnormal liver function tests (\> 2 times upper limit of normal range)).
* Requirement for medication known to influence blood pressure and/or heart rate and/or gastrointestinal function, drugs with anticholinergic effects
* Alcohol consumption \> 20 g per day
* Smoking \> 10 cigarettes per day
* Pregnancy or lactation.
* Vegetarian
* Allergy to sitagliptin or any other 'gliptin'.
* Donation of blood within the previous 3 months
* Participation in any other research studies within the previous 3 months
* Exposure to ionising radiation for research purposes in the previous 12 months
* Inability to give informed consent

Primary outcomes:
measure: Gastric emptying
timeFrame: 3 hours per gastric emptying study (i.e. 6 hours)
Secondary outcomes:
measure: Glycaemia
timeFrame: 4 hours during each gastric empty study (i.e. 8 hours)
measure: Gastrointestinal hormone release
timeFrame: 4 hours during each gastric empty study (i.e. 8 hours)
measure: Intragastric meal distribution
timeFrame: 3 hours during each gastric empty study (i.e. 6 hours)
measure: Blood pressure
timeFrame: 4.5 hours during each gastric empty study (i.e. 9 hours)
measure: Heart rate
timeFrame: 4.5 hours during each gastric empty study (i.e. 9 hours)
measure: Splanchnic blood flow
timeFrame: 4 hours during each gastric empty study (i.e. 8 hours)
measure: Cardiac output
timeFrame: 4 hours during each gastric empty study (i.e. 8 hours)
measure: Stroke volume
timeFrame: 4 hours during each gastric empty study (i.e. 8 hours)
measure: Appetite
timeFrame: 4 hours during each gastric empty study (i.e. 8 hours)
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: University of Adelaide, Discipline of Medicine, Royal Adelaide Hospital
state: South Australia
Study officials:
affiliation: University of Adelaide
name: Karen L Jones, DAppSci, PhD
role: PRINCIPAL_INVESTIGATOR
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