None listed
Conditions
Brief summary
This study is designed to evaluate the effects of 8 weeks treatment with the glucagon-like peptide-1 agonist, exenatide (once weekly (QW)), on the rate of stomach emptying, glucose absorption and blood glucose and plasma insulin concentrations in type 2 diabetes. This is a randomised parallel designed study. Subjects recruited into the study who pass screening criteria will be randomised to receive exenatide QW or matching placebo. They will have a gastric emptying study performed using the gold standard technique (scintigraphy) at baseline and at 8 weeks. Immediately following the first gastric emptying study they will commence treatment with exenatide QW or Placebo, administered subcutaneously at weekly intervals. Glucose absorption, blood pressure, blood glucose and plasma insulin will be assessed during each of the gastric emptying measurements.
Interventions
1. Exenatide QW 2mg or Exenatide Placebo to be injected, subcutaneously, once a week for 8 weeks. The injection is administered by one of the investigators to remove any issues relating to compliance.
2. A gastric emptying study using the gold standard technique (scintigraphy) will be performed at baseline and at 8 weeks. The carbohydrate meal used to measure gastric emptying rate is a standardised mashed potato meal (369 kcal) comprising 65g powdered potato and 20g glucose reconstituted with 2
1. Exenatide QW 2mg or Exenatide Placebo to be injected, subcutaneously, once a week for 8 weeks. The injection is administered by one of the investigators to remove any issues relating to compliance. 2. A gastric emptying study using the gold standard technique (scintigraphy) will be performed at baseline and at 8 weeks. The carbohydrate meal used to measure gastric emptying rate is a standardised mashed potato meal (369 kcal) comprising 65g powdered potato and 20g glucose reconstituted with 250ml boiling water and labelled with 20 MBq 99mTc-sulphur colloid and will include 5g 3-O-methylglucose (3-O-MG, Sigma Aldrich, USA). This equates to an effective radiation dose of 0.5mSv per study. On one occasion, at t=240 minutes, the volunteer will drink 100 ml of water labelled with 4MBq of 99mTc-sulphur colloid and a lateral image of the stomach will be acquired to derive correction factors for gamma ray attenuation. This equates to a total dose of 1.1mSv (including the lateral dose), which is within The RAH Radiation Safety Guidelines (upper limit 5mSv) and has been approved previously by the Research Ethics Committee of the Royal Adelaide Hospital.
Sponsors
University of Adelaide
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female participants aged 40 – 80 years 2. Female subjects who are post-menopausal; or pre-menopausal with surgical contraception (such as tubal ligation) or an intrauterine device. Pre-menopausal women will require a confirmed negative urine ß-hCG pregnancy test at screening visit. 3. T2DM (World Health Organisation (WHO) criteria) managed by diet alone or on metformin 4. Glycated haemoglobin (HbA1c) greater than or equal to 6.0% and less than 8.5%, in the last 4 months prior to enrolment in the study 5. Body mass index (BMI) 25 – 35 kg/m2 6. Haemoglobin and ferritin in the normal range for gender and age. 7. Participant has provided written informed consent.
Exclusion criteria
1. Evidence of renal disease (i.e. a creatinine clearance cut-off of less than 50 ml/min. Calculated creatinine clearance will be determined as follows using the Cockcroft-Gault equation: Cr clearance = [140 - age (years) x weight (kg)] / [0.814 x serum creatinine (µmol/L)] (For female subjects, multiply Cr clearance x 0.85)13) 2. Iron stores, or liver function tests outside the following ranges: Alanine aminotransferase (ALT) less than 55 U/L Alkaline phosphatase (ALP) 30 - 110 U/L Aspartate transaminase (AST) less than 45 U/L Total bilirubin 6 - 24 µmol/L Haemoglobin 115 – 155 g/L (Females); 135 – 172 g/L (Males) Ferritin 15 – 200 µg/L (Females); 30 – 300 µg/L (Males) 3. Hepatic or cardiovascular disease, pancreatitis (subjects with past history of acute or chronic pancreatitis, gastric surgery, or known gastroparesis on history or screening biochemistry tests. 4. Participants with any history of cancer, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy at least 12 months prior to screening or other malignancies treated with apparent success with curative therapy at least 5 years prior to screening will be excluded. 5. History of any clinically significant disease or disorder which may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer’s ability to participate in the study. 6. Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 7. History of hyperthyroidism or uncontrolled hypothyroidism. 8. Chronic gastrointestinal symptoms as assessed by questionnaire. 9. Use of drugs potentially affecting gastrointestinal motility (nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids; histamine-2 receptor antagonists, anti-emetics (dopamine antagonists, 5HT-3 receptor antagonists), laxatives, prokinetic agents, anticholinergic agents, cholinergic agents, opioid medications, erythromycin). 10.Current use of anticoagulants. 11. Inability to abstain from smoking for 12 hours prior to the gastric emptying tests. 12. Consumption of more than 2 units alcohol daily on a regular basis. 13. Known or suspected history of alcohol or drug abuse, as judged by the Investigator. 14. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to exenatide or drugs with a similar chemical structure or its components. 15. Known hypersensitivity to IV infusion equipment, plastics, adhesive or silicone, or know history of hypotension or infusion site reactions with IV administration of other medicines 16. Participation in any research studies involving exposure to ionising radiation within the previous 12 months 17. Donated blood in the past 3 months
Outcome results
None listed