Trial Review

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12613000843752
Ethics application status
Not yet submitted
Date submitted
19/07/2013
Date registered
31/07/2013
Date last updated
31/07/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Molecular determinants of glucose sensing in human gastrointestinal tract of patients with type 2 diabetes and healthy volunteers.
Scientific title
In patients with type 2 diabetes as opposed to healthy volunteers, what will the GLP-1 release and expression of glucose sensing molecules be in functionally identified colonic cells, activated by glucose or glibenclamide
Secondary ID [1] 282862 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type II Diabetes 289674 0
Condition category
Condition code
Metabolic and Endocrine 289992 289992 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ARM 1: Patients with Type II Diabetes
After an overnight fast, a 1000 mL normal saline enema will be given by a registered nurse to cleanse the distal bowel. An intravenous cannula will be inserted into a forearm vein on each arm, one for blood sampling and the other for infusion of 25% glucose at a variable rate to maintain the blood glucose concentration = 5 mmol/L. The participant will then have the unsedated flexible sigmoidoscopy performed in the left lateral position using a flexible video colonoscope inserted first to the rectum, where four mucosal biopsies will be collected using biopsy forceps. The scope will then be advanced to the descending colon, where four additional biopsies will be collected. The colon will be perfused with a solution containing 3mg glibenclamide made up to 120 mL with normal saline (a 50 micromolar solution) At T=30 min, four additional biopsies will be collected from each site (total 16 biopsies per subject) and then the colonoscope will be withdrawn. A high carbohydrate meal with approx 45g of carbohydrates will be provided at T=120min, at which time the variable IV glucose infusion will cease and the subject will be observed for a further 6 hours with meals of sandwiches provided at 3 hourly intervals.
ARM 2 - Healthy Control
These people will undergo the same intervention and comparator treatment as those with diabetes.
Intervention code [1] 287558 0
Treatment: Drugs
Comparator / control treatment
For both arms of the study, the 2 study visits (intervention and the comparator) will be separated by at least 1 week.

The comparator treatment is exactly the same as the intervention treatment, however instead of the infusion of 3mg of glibencamide, a glucose solution (30 g glucose, made up to a total volume of 120 mL with water) will be infused via the endoscopic biopsy channel and continued at a rate of 4 kcal/min for 30 min.
Control group
Active

Outcomes
Primary outcome [1] 290040 0
Transcript levels and localisation of nutrient GPCR for carbohydrate sensing, and ion channels, in the mucosa and functionally identified cells of the human colon, measured from the biopsies taken during the study.
Timepoint [1] 290040 0
Biopsies taken at t = 0 and 30.
Primary outcome [2] 290041 0
GLP-1 responses to colonic perfusion with glucose or glibenclamide in healthy and type 2 patients (area-under-the curve; AUC), as measured by blood samples taken throughout the study.
Timepoint [2] 290041 0
Bloods taken at T = 0, 10, 20, 30, 40, 50, 60, 80, 100, and 120 min
Primary outcome [3] 290042 0
Differences in the GLP-1 responses, and distribution and levels of these targets between patients with type 2 diabetes and healthy subjects, as measured by differences in results from the blood samples.
Timepoint [3] 290042 0
Blood samples analysed once study is complete
Secondary outcome [1] 303826 0
The effects of glucose or glibencamide infusion on glucagon, C peptide, GLP-2, and PYY concentrations, as measured by concentrations in blood samples taken throughout the study.
Timepoint [1] 303826 0
Bloods taken at T = 0, 10, 20, 30, 40, 50, 60, 80, 100, and 120 min

Eligibility
Key inclusion criteria
Patients with type 2 diabetes (World Health Organisation (WHO) criteria) managed by diet alone or metformin, with a HbA1c =/< 7.5%.
Healthy volunteers, matched as closely as possible to the diabetic subjects for age, sex, and body mass index.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Significant illness other than diabetes, including impairment to cardiovascular or respiratory function that limits a subject’s activity and therefore would represent a risk to undertaking endoscopy safely (American Society of Anesthesiologists Grade 3 or more)
History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms (as assessed by a validated upper gastrointestinal symptom questionnaire, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy)
Haemoglobin below the lower limit of the normal range (ie. <135g/L for men and 115g/L for women), and ferritin below the lower limit of normal (ie. <10mcg/L)
Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests (> 2 times upper limit of normal))
History of severe respiratory, cardiovascular, hepatic and/or renal disease, chronic alcohol abuse or epilepsy (excluded by history)
Subjects requiring medication that may influence gastrointestinal function
Any patient with coagulopathy.
Allergy to glibencamide and/or sulphonamide derivatives
Patients with Thrombocytopenia
Patients requiring treatment with anticoagulants, anti-platelet agents and NSAIDS
Presence of mucosal abnormalities at sigmoidoscopy such as inflammatory bowel disease and colorectal cancer.
Body mass index greater than 32 kg/m2
Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes per day
Female patients not using appropriate contraceptive method (ie oral contraceptive pill, diaphragm, Depo-Provera hormonal contraceptive injection, intrauterine device (IUD), Norplant method)
Vegetarian, lactation, or pregnancy (verified by urine testing in women of reproductive age; in these subjects, the study will be completed during the follicular phase of the menstrual cycle)
Donation of blood within the previous 3 months
Participation in any other research studies within the previous 3 months

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/09/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 1346 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 7179 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 287641 0
Hospital
Name [1] 287641 0
Royal Adelaide Hospital
Department of Gastroenterolog and Hepatology
Country [1] 287641 0
Australia
Primary sponsor type
Individual
Name
Dr. Nam Q Nguyen
Address
Department of Gastroenterolog and Hepatology
Royal Adelaide Hospital
Level 7 Q7 North Wing
North Terrace
Adelaide 5000 SA
Country
Australia
Secondary sponsor category [1] 286382 0
None
Name [1] 286382 0
Address [1] 286382 0
Country [1] 286382 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 289611 0
The Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 289611 0
Ethics committee country [1] 289611 0
Australia
Date submitted for ethics approval [1] 289611 0
22/07/2013
Approval date [1] 289611 0
Ethics approval number [1] 289611 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41554 0
Dr Nam Nguyen
Address 41554 0
Department of Gastroenterology and Hepatology, Q7 Level 7 North Wing Royal Adelaide Hospital North Terrace Adelaide SA 5000
Country 41554 0
Australia
Phone 41554 0
+61 8 8222 2412
Fax 41554 0
Email 41554 0
[email protected]
Contact person for public queries
Name 41555 0
Nam Nguyen
Address 41555 0
Department of Gastroenterology and Hepatology, Q7 Level 7 North Wing Royal Adelaide Hospital North Terrace Adelaide SA 5000
Country 41555 0
Australia
Phone 41555 0
+61 8 8222 2412
Fax 41555 0
Email 41555 0
[email protected]
Contact person for scientific queries
Name 41556 0
Nam Nguyen
Address 41556 0
Department of Gastroenterology and Hepatology, Q7 Level 7 North Wing Royal Adelaide Hospital North Terrace Adelaide SA 5000
Country 41556 0
Australia
Phone 41556 0
+61 8 8222 2412
Fax 41556 0
Email 41556 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.