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Trial registered on ANZCTR


Registration number
ACTRN12608000433303
Ethics application status
Approved
Date submitted
11/08/2008
Date registered
29/08/2008
Date last updated
6/11/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of sitagliptin, a dipeptidyl peptidase IV (DPP IV) inhibitor, on blood glucose and plasma incretin and insulin responses to small intestinal glucose infusion, in healthy lean and obese subjects, and alone or in combination with metformin in patients with type 2 diabetes mellitus.
Scientific title
Effects of sitagliptin, a dipeptidyl peptidase IV (DPP IV) inhibitor, on blood glucose and plasma incretin and insulin responses to small intestinal glucose infusion, in healthy lean and obese subjects, and alone or in combination with metformin in patients with type 2 diabetes mellitus.
Secondary ID [1] 283533 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes mellitus 3532 0
Incretin hormone secretion and metabolism 3533 0
Condition category
Condition code
Metabolic and Endocrine 3685 3685 0 0
Diabetes
Metabolic and Endocrine 3686 3686 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Healthy lean and obese subjects will each undergo two studies (sitagliptin 100 mg oral versus control), in double-blind, randomised fashion, separated by 3 - 14 days. Patients with type 2 diabetes will be studied on 4 occasions each: twice during therapy with metformin 850 mg twice daily for 7 days (days 5 and 8, sitagliptin 100 mg oral or control), and twice during treatment with a matching placebo twice daily for 7 days, with a washout period of 14 days between treatment periods. In the diabetic patients, the order of both metformin and placebo, and sitagliptin and control, will be randomised, except that during the second metformin/placebo treatment period, the order of sitagliptin and control will be identical to the first treatment period. On each study day, glucose will be infused into the duodenum at 2 kcal/min from 0 to 120 min. Within each group (healthy lean, healthy obese, diabetic), each subjects acts as his own control, but comparison will also be made between groups.
Intervention code [1] 3247 0
Treatment: Drugs
Comparator / control treatment
Control tablet identical in size, colour and taste to sitagliptin tablet. Placebo tablet identical in size, colour and taste to metformin tablet.
Control group
Placebo

Outcomes
Primary outcome [1] 4593 0
Blood glucose concentration
Timepoint [1] 4593 0
At -30, 0, 5, 15, 30, 45, 60, 75, 90, 120, and 150 min on each study day
Primary outcome [2] 4594 0
Plasma total and intact glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) concentrations
Timepoint [2] 4594 0
At -30, 0, 5, 15, 30, 45, 60, 75, 90, 120, and 150 min on each study day
Primary outcome [3] 4595 0
Plasma insulin concentration
Timepoint [3] 4595 0
At -30, 0, 5, 15, 30, 45, 60, 75, 90, 120, and 150 min on each study day
Secondary outcome [1] 7753 0
Appetite scores, using 100 mm visual analog scales
Timepoint [1] 7753 0
At -30, 0, 5, 15, 30, 45, 60, 75, 90, 120, and 150 min on each study day
Secondary outcome [2] 7754 0
Food intake (grams and kcal consumed from a buffet meal)
Timepoint [2] 7754 0
30 minute buffet meal given at 120 min on each study day
Secondary outcome [3] 7755 0
Frequency of antral and pyloric contractions measured by manometry catheter
Timepoint [3] 7755 0
During 15 min periods between 0 and 120 min on each study day

Eligibility
Key inclusion criteria
Healthy lean subjects:
1. Male Causcasians aged 18 – 70 years, age-matched to the obese subjects
2. Body mass index (BMI) 19 - 25 kg/m2
Healthy obese subjects:
1. Male Causcasians aged 18 – 70 years
2. Body mass index (BMI) 30 - 40 kg/m2
3. Fasting blood glucose concentration < 5.6 mmol/L
Type 2 diabetic patients:
1. Male Causcasians aged 18 – 70 years
2. Body mass index (BMI) 28 - 40 kg/m2
3. Type 2 diabetes (World Health Organisation (WHO) criteria) managed by diet alone (i.e no oral hypoglycaemic drugs or insulin)
4. Glycated haemoglobin = 6.0% and < 8.5%
Minimum age
18 Years
Maximum age
70 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of gastrointestinal surgery (except appendicectomy)
2. Medication which may affect gastrointestinal motor function, body weight or appetite
3. Other significant illness, including epilepsy, cardiovascular or respiratory disease
4. Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes per day
5. Regular gastrointestinal symptoms (as assessed by a validated upper gastrointestinal symptom questionnaire)
6. Autonomic nerve damage (as assessed by standardised cardiovascular reflex tests)
7. Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests)
8. For diabetic patients, inability to tolerate oral metformin 850 mg bd for a 7 day trial, to be completed at least 2 weeks prior to commencing the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer-generated random number table
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 3714 0
Commercial sector/Industry
Name [1] 3714 0
Merck Sharpe & Dohme (Australia) Pty Ltd
Address [1] 3714 0
54-68 Ferndell Street, South Granville NSW 2142
Country [1] 3714 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
North Terrace, Adelaide 5000
Country
Australia
Secondary sponsor category [1] 3331 0
None
Name [1] 3331 0
Address [1] 3331 0
Country [1] 3331 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5769 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 5769 0
Level 3, Hanson Institute
Royal Adelaide Hospital, North Terrace, Adelaide 5000
Ethics committee country [1] 5769 0
Australia
Date submitted for ethics approval [1] 5769 0
Approval date [1] 5769 0
28/04/2008
Ethics approval number [1] 5769 0
080419

Summary
Brief summary
This study will determine whether the antidiabetic medicine, sitagliptin, has the capacity to increase intestinal hormones called glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), decrease blood glucose levels and reduce appetite in healthy subjects and people with type 2 diabetes. We will also determine, in the people with diabetes, whether these effects are enhanced when sitagliptin is given together with another diabetes drug, metformin.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28826 0
A/Prof Chris Rayner
Address 28826 0
Discipline of Medicine Royal Adelaide Hospital North Terrace Adelaide SA 5000
Country 28826 0
Australia
Phone 28826 0
+61 8 82222916
Fax 28826 0
Email 28826 0
chris.rayner@adelaide.edu.au
Contact person for public queries
Name 11983 0
A/Prof A/Prof Chris Rayner
Address 11983 0
Discipline of Medicine
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country 11983 0
Australia
Phone 11983 0
08 8222 2916
Fax 11983 0
08 8223 3870
Email 11983 0
chris.rayner@adelaide.edu.au
Contact person for scientific queries
Name 2911 0
A/Prof A/Prof Chris Rayner
Address 2911 0
Discipline of Medicine
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country 2911 0
Australia
Phone 2911 0
08 8222 2916
Fax 2911 0
08 8223 3870
Email 2911 0
chris.rayner@adelaide.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary