E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The brainメ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. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of a single dose of the GLP-1 agonist Exenatide on the brainメ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. |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Regional Brain activation in response to food ingestion. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 0 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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After analysing the response to exenatide in 12 Type 2 diabetics. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |