The brain?s response to food ingestion can be imaged and preliminary data suggest that these responses are different in the obese and insulin resistant. We will investigate the hypothesis that Exenatide will normalize neuronal activation in brain regions concerned with food seeking behaviour, appetite control and reward motivated behaviours (pre-frontal cortex, amygdala and insula) in response to nutrient ingestion in Type 2 diabetes.
Conditions
Interventions
Trade Name: Byetta 10microgram solution for injection, prefilled pen
Pharmaceutical Form: Injection*
Other descriptive name: Exenatide 10 microgram in 40 microlitres = 0.25 mg/ml
Concentration unit: m
Sponsors
King's College Hospital
King's College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: People with Type 2 diabetes: 1. 18-65 years of age 2. Type 2 diabetes, with evidence of residual insulin secretion and insulin resistance as determined by absence of requirement for insulin therapy 3. HbA1c ("gold standard" blood glucose control measure) 5.5-9.0% 4. Diabetes controlled by either diet and exercise +/- combination of oral hypoglycaemic therapy (Metformin, Sulphonylurea, Meteglinides and/or thiazolidinediones. 5. Diabetes therapy unchanged for three months prior to the study 6. Clear understanding of written and spoken English 7. Ability to given written consent Healthy volunteers (subjects without diabetes for generation of normative data with this scanning protocol):18-65 years of age with no significant medical history and not taking regular medications, who have a clear understanding of written and spoken English and are able to given written consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Uncontrolled hypertension (blood pressure) 2. Unstable diabetes control as judged by the investigator 3. Insulin treated diabetes 4. Cardiac failure (NYHA Grade 2 or higher - objective measure of heart failure) 5. Inabililty fully to comprehend verbal and written English/understand the protocol 6. Left handed subjects 7. Weight >120kg. 8. Contraindictation to fMRI scanning (metal implants; shrapnel injuries; cardiac pacemaker; claustrophobia) 9. Subjects who suffer from claustrophobia 10. Needle phobic subjects 11. Patients taking recreational drugs 12. Patients who have received any investigational drugs in the past 3 months. 13. Pregnant females or those actively trying to become pregnant 14. Subjects at high risk or with blood bourne infectious disease, such as HIV, Hepatitis B/C.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Regional Brain activation in response to food ingestion. ;Main Objective: To assess the effect of a single dose of the GLP-1 agonist Exenatide on the brain?s response to nutrient ingestion in people with insulin resistant Type 2 diabetes, using functional magnetic resonance imaging (fMRI). GLP-1 is an incretin and also a satiety hormone and its secretion is suboptimal in Type 2 diabetes. Exenatide improves diabetes control at the same time as encouraging weight loss. This study investigates the hypothesis that Exenatide, as a single dose, will enhance neuronal activation in response to oral nutrient ingestion in people with Type 2 diabetes, especially in brain areas known to be involved in food seeking behaviour and appetite. We will include a group of healthy volunteers in a non-drug treated control protocol, to establish the normal brain response to food ingestion as a comparator.;Secondary Objective: 1)To assess the effects of a single dose of exenatide vs placebo on the magnitude of the glucose and insulin changes in response to a standardised nutrient challenge in the acute study 2)To assess both the short term effects of exenatide or placebo on satiety responses to a standardised nutrient ingestion challenge 3)To assess the short term effects of exenatide on the brain responses to food imagery | — |
Countries
United Kingdom
Outcome results
None listed