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Effects of Sitagliptin on Gastric Emptying, Glycaemia and Blood Pressure in Type 2 Diabetes

Primary Purpose

Gastroparesis, Diabetes Mellitus

Status
Completed
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Sitagliptin
Placebo
Sponsored by
Royal Adelaide Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastroparesis focused on measuring gastric emptying, glycemia, appetite, incretin hormones

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Adelaide, Discipline of Medicine, Royal Adelaide Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sitaglipltin (100mg)

Placebo (sugar pill)

Arm Description

Active drug (sitagliptin)

Inactive drug (placebo)

Outcomes

Primary Outcome Measures

Gastric emptying
Gastric retention (percent in the total stomach)

Secondary Outcome Measures

Glycaemia
blood glucose (mmol/L) and plasma insulin (mU/L)
Gastrointestinal hormone release
GLP-1, GIP, C-peptide, 3-OMG
Intragastric meal distribution
percent retention in the proximal and distal stomach
Blood pressure
systolic and diastolic blood pressure (mmHg)
Heart rate
Heart rate (beats per minute)
Splanchnic blood flow
Doppler ultrasound of superior mesenteric artery flow (ml/min)
Cardiac output
Finapres (L)
Stroke volume
Finapres (mL)
Appetite
visual analogue questionnaire to assess hunger, fullness, desire to eat (mm)

Full Information

First Posted
December 16, 2014
Last Updated
July 5, 2017
Sponsor
Royal Adelaide Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02324010
Brief Title
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

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Royal Adelaide Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroparesis, Diabetes Mellitus
Keywords
gastric emptying, glycemia, appetite, incretin hormones

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sitaglipltin (100mg)
Arm Type
Experimental
Arm Description
Active drug (sitagliptin)
Arm Title
Placebo (sugar pill)
Arm Type
Placebo Comparator
Arm Description
Inactive drug (placebo)
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Other Intervention Name(s)
MK-0431-075, Januvia
Intervention Description
100mg mane for 2 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar pill
Intervention Description
Inactive drug (Placebo)
Primary Outcome Measure Information:
Title
Gastric emptying
Description
Gastric retention (percent in the total stomach)
Time Frame
3 hours per gastric emptying study (i.e. 6 hours)
Secondary Outcome Measure Information:
Title
Glycaemia
Description
blood glucose (mmol/L) and plasma insulin (mU/L)
Time Frame
4 hours during each gastric empty study (i.e. 8 hours)
Title
Gastrointestinal hormone release
Description
GLP-1, GIP, C-peptide, 3-OMG
Time Frame
4 hours during each gastric empty study (i.e. 8 hours)
Title
Intragastric meal distribution
Description
percent retention in the proximal and distal stomach
Time Frame
3 hours during each gastric empty study (i.e. 6 hours)
Title
Blood pressure
Description
systolic and diastolic blood pressure (mmHg)
Time Frame
4.5 hours during each gastric empty study (i.e. 9 hours)
Title
Heart rate
Description
Heart rate (beats per minute)
Time Frame
4.5 hours during each gastric empty study (i.e. 9 hours)
Title
Splanchnic blood flow
Description
Doppler ultrasound of superior mesenteric artery flow (ml/min)
Time Frame
4 hours during each gastric empty study (i.e. 8 hours)
Title
Cardiac output
Description
Finapres (L)
Time Frame
4 hours during each gastric empty study (i.e. 8 hours)
Title
Stroke volume
Description
Finapres (mL)
Time Frame
4 hours during each gastric empty study (i.e. 8 hours)
Title
Appetite
Description
visual analogue questionnaire to assess hunger, fullness, desire to eat (mm)
Time Frame
4 hours during each gastric empty study (i.e. 8 hours)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen L Jones, DAppSci, PhD
Organizational Affiliation
University of Adelaide
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Adelaide, Discipline of Medicine, Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia

12. IPD Sharing Statement

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Effects of Sitagliptin on Gastric Emptying, Glycaemia and Blood Pressure in Type 2 Diabetes

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