fMRI of Hypothalamic Responses to Taste, Temperature and Glucose

Study Overview
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Brief Summary
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The study will consist of five occasions with one week in between. BOLD signal intensity of the hypothalamus will be measured using fMRI. Measurements will be done before and after drinking 300 ml plain water or water to which glucose and/or ethyl butyrate will be added.

Detailed Description
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The hypothalamus is known to be important for control of feeding behaviour as well as the regulation of temperature. Functional magnetic resonance imaging (fMRI) is a non-invasive method, which detects transient haemodynamic changes in the brain, using blood oxygen level dependent (BOLD) signal differences. In order to investigate the role of hypothalamic neural activity in response to taste, glucose and temperature, fMRI will be performed before, during and after ingestion of 300 ml plain water or water with added ethyl butyrate (pineapple flavour), added glucose or added ethyl butyrate plus glucose. All beverages will be consumed at 22 °C and the combination will also be drunk at 0 °C. The study uses a randomised cross-over design in 16 healthy male subjects with a normal body weight. There will be an interval of at least one week between the five occasions. BOLD signal intensity of the hypothalamus will be continuously measured for 21 minutes (5 minutes baseline, 4 minutes during drinking and 12 minutes after drinking).

Official Title
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Functional Magnetic Resonance Imaging of Human Hypothalamic Responses to Taste, Temperature and Glucose Sensing

Conditions
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Healthy

Intervention / Treatment
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* Other: Water
* Other: Glucose
* Other: Ethyl butyrate
* Other: Glucose + ethyl butyrate
* Other: Glucose + ethyl butyrate 0 C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age between 18 and 25 years BMI between 20 and 23 kg/m2 Length between 170 and 190 centimetres Exclusion Criteria: Diabetes or history of other disturbances of glucose metabolism (eg impaired glucose tolerance, hypoglycaemia). Any genetic or psychiatric disease (e.g. fragile X syndrome, major depression) affecting brain Any significant chronic disease Renal or hepatic disease Recent weight changes or attempts to lose weight (> 3 kg weight gain or loss, within the last 3 months) Smoking (current or last 6 months) Alcohol consumption of more than 21 units per week or use of recreational drugs at present or in the last year Recent blood donation (within the last 2 months) Recent participation in other biomedical research projects (within the last 3 months), participation in 3 or more biomedical research projects in one year Contra-indication to MRI scanning: Claustrophobia Pacemakers and defibrillators Nerve stimulators Intracranial clips Intraorbital or intraocular metallic fragments Cochlear implants Ferromagnetic implants

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Water/gluc/gluc+EB/EB/gluc+EB_cold<br>First Water 22 C, then Glucose 22 C, then Glucose + Ethyl butyrate 22 C, then Ethyl butyrate 22 C and then Glucose + Ethyl butyrate 0 C | Other: Water<br>* Water, 300 ml, at room temperature<br>Other: Glucose<br>* Water containing 50 g glucose, 300 ml, at room temperature<br>Other: Ethyl butyrate<br>* Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate 0 C<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade<br>|
| Experimental: Water/gluc+EB/gluc/gluc+EB_cold/EB<br>First Water 22 C, then Glucose + Ethyl butyrate 22 C, then Glucose 22 C, then Glucose + Ethyl butyrate 0 C and then Ethyl butyrate 22 C | Other: Water<br>* Water, 300 ml, at room temperature<br>Other: Glucose<br>* Water containing 50 g glucose, 300 ml, at room temperature<br>Other: Ethyl butyrate<br>* Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate 0 C<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade<br>|
| Experimental: Gluc/water/EB/gluc+EB/glucose+EB_cold<br>First Glucose 22 C, then Water 22 C, then Ethyl butyrate 22 C, then Glucose + Ethyl butyrate 22 C and then Glucose + Ethyl butyrate 0 C | Other: Water<br>* Water, 300 ml, at room temperature<br>Other: Glucose<br>* Water containing 50 g glucose, 300 ml, at room temperature<br>Other: Ethyl butyrate<br>* Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate 0 C<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade<br>|
| Experimental: Gluc/EB/water/gluc+EB_cold/gluc+EB<br>First Glucose 22 C, then Ethyl butyrate 22 C, then Water 22 C, then Glucose + Ethyl butyrate 0 C and then Glucose + Ethyl butyrate 22 C | Other: Water<br>* Water, 300 ml, at room temperature<br>Other: Glucose<br>* Water containing 50 g glucose, 300 ml, at room temperature<br>Other: Ethyl butyrate<br>* Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate 0 C<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade<br>|
| Experimental: EB/Gluc/gluc+EB_cold/water/glucose+EB<br>First Ethyl butyrate 22 C, then Glucose 22 C, then Glucose + Ethyl butyrate 0 C, then Water 22 C and then Glucose + Ethyl butyrate 22 C | Other: Water<br>* Water, 300 ml, at room temperature<br>Other: Glucose<br>* Water containing 50 g glucose, 300 ml, at room temperature<br>Other: Ethyl butyrate<br>* Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate 0 C<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade<br>|
| Experimental: EB/gluc+EB_cold/gluc/glucose+EB/water<br>First Ethyl butyrate 22 C, then Glucose + Ethyl butyrate 0 C, then Glucose 22 C, then Glucose + Ethyl butyrate 22 C and then Water 22 C | Other: Water<br>* Water, 300 ml, at room temperature<br>Other: Glucose<br>* Water containing 50 g glucose, 300 ml, at room temperature<br>Other: Ethyl butyrate<br>* Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate 0 C<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade<br>|
| Experimental: Gluc+EB_cold/water/glucose+EB/glucose/EB<br>First Glucose + Ethyl butyrate 22 C, then Water 22 C, then Glucose + Ethyl butyrate 0 C, then Glucose 22 C and then Ethyl butyrate 22 C | Other: Water<br>* Water, 300 ml, at room temperature<br>Other: Glucose<br>* Water containing 50 g glucose, 300 ml, at room temperature<br>Other: Ethyl butyrate<br>* Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate 0 C<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade<br>|
| Experimental: Gluc+EB_cold/glucose+EB/water/EB/glucose<br>First Glucose + Ethyl butyrate 22 C, then Glucose + Ethyl butyrate 0 C, then Water 22 C, then Ethyl butyrate 22 C and then Glucose 22 C | Other: Water<br>* Water, 300 ml, at room temperature<br>Other: Glucose<br>* Water containing 50 g glucose, 300 ml, at room temperature<br>Other: Ethyl butyrate<br>* Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate 0 C<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade<br>|
| Experimental: Gluc+EB_cold/gluc+EB/EB/water/glucose<br>First Glucose + Ethyl butyrate 0 C, then Glucose + Ethyl butyrate 22 C, then Ethyl butyrate 22 C, then Water 22 C and then Glucose 22 C | Other: Water<br>* Water, 300 ml, at room temperature<br>Other: Glucose<br>* Water containing 50 g glucose, 300 ml, at room temperature<br>Other: Ethyl butyrate<br>* Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate 0 C<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade<br>|
| Experimental: Gluc+EB_cold/EB/gluc+EB/glucose/water<br>First Glucose + Ethyl butyrate 0 C, then Ethyl butyrate 22 C, then Glucose + Ethyl butyrate 22 C, then Glucose 22 C and then Water 22 C | Other: Water<br>* Water, 300 ml, at room temperature<br>Other: Glucose<br>* Water containing 50 g glucose, 300 ml, at room temperature<br>Other: Ethyl butyrate<br>* Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature<br>Other: Glucose + ethyl butyrate 0 C<br>* Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine hypothalamic function in response to taste, temperature and glucose sensing | BOLD-signal intensity | Before (5 minutes) and after (12 minutes) drinking |