Clinical trial NCT00501657: Effects of Sitagliptin on Gastric Emptying in Healthy Subjects
Official title: Effects of Sitagliptin on Gastric Emptying in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastroparesis
Diabetes Mellitus
Keywords: gastric emptying
glycemia
appetite
incretin hormones
Lead sponsor: Royal Adelaide Hospital
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2007-07-16
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effects of the drug, sitagliptin, on the rate at which the stomach empties, and the release of gut hormones and blood glucose concentrations, after a mashed potato meal in healthy subjects. Sitagliptin has been shown to reduce the blood glucose (sugar) response to a meal and this may potentially be due to slowing of stomach emptying. This is particularly relevant to people who have diabetes, in whom normalization of elevated blood glucose levels is important to maintain health.

Detailed description: The purpose of this study is to evaluate the effect of sitagliptin on gastric emptying, intragastric meal distribution, postprandial glycemia and insulinemia in healthy subjects. Glucagon-like peptide-1 (GLP-1) inhibits gastric emptying, thereby slowing the delivery of nutrients, and their absorption, across the small intestine. 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 glycemic response to, a carbohydrate-containing meal.

Fifteen 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 and appetite will be measured for 4 hours following ingestion of a mashed potato meal.

Eligibility criteria: Inclusion Criteria:

* Male or female (females must be using an appropriate contraceptive method)
* 18 - 45 years
* Body mass index (BMI) 19 - 25 kg/m2.

Exclusion criteria:

* Subjects with gastrointestinal disease, history of gastrointestinal surgery and/or significant gastrointestinal symptoms
* Subjects taking medication known to influence gastrointestinal function
* Alcohol intake \> 20 g per day
* Smoking \> 10 cigarettes per day
* Pregnant and/or lactating females
* Calculated creatinine clearance \< 60 ml/min
* Exposure to ionising radiation for research purposes in the previous 12 months.

Primary outcomes:
measure: Gastric emptying rate
timeFrame: 4 hours per study
Secondary outcomes:
measure: Intragastric distribution, gastrointestinal hormone release (GLP-1, GIP), glycemia, insulinemia, appetite
timeFrame: 4 hours per study
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Discipline of Medicine, Royal Adelaide Hospital
state: South Australia
Study officials:
affiliation: University of Adelaide, Royal Adelaide Hospital
name: Karen L Jones, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stevens JE, Horowitz M, Deacon CF, Nauck M, Rayner CK, Jones KL. The effects of sitagliptin on gastric emptying in healthy humans - a randomised, controlled study. Aliment Pharmacol Ther. 2012 Aug;36(4):379-90. doi: 10.1111/j.1365-2036.2012.05198.x. Epub 2012 Jun 28.