Raclopride-PET/MRT

Study Overview
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Brief Summary
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Cerebral insulin resistance plays an important role in the development of obesity and diabetes mellitus type 2. The aim of this project is to examine the effect of human nasal insulin on the dopaminergic system. Therefore, characteristics of cerebral dopamine receptors before and after administration of nasal insulin vs. placebo shall be analyzed in a randomized way. Moreover, the investigators plan to examine the insulin action on cortical and subcortical activation in humans and the interaction of dopamine metabolism with [11C]-Raclopride-PET/MRI. By performing fMRI measurements, insulin sensitivity of the central nervous system can be investigated simultaneously. Recruiting is planed as a two-step process.First 12 normal-weight (BMI 20-25 kg/m²) men should be examined. If first results show a insulin-dependent effect on the availability of dopamine receptors in the human brain, recruitment of 12 overweight men will get started.

Official Title
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Characterization of Insulin Action and Dopamine-signaling in the Human Brain of Normal Weight and Obese Subjects by [11C]-Raclopride-PET/MRT

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Other: intranasal insulin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures. Intake of any medication HbA1C <6% BMI 20-25 kg/m² Clinical routine blood parameters within the normal ranges All participants must agree to get informed of unexpected detected, clinical relevant findings. Exclusion Criteria: Acute diseases such as infections (e.g.) Any relevant cardiovascular disease Any surgery within the last three months Any neurologic or psychiatric disease Known allergies Hb < 13 g/dl Presence of any contraindication for the conduct of an MRI investigation, such as cardiac pacemakers, ferromagnetic haemostatic clips in the central nervous system, metallic splinters in the eye, ferromagnetic or electronically operated active devices like automatic cardioverter defibrillators, cochlear implants, insulin pumps and nerve stimulators, prosthetic heart valves etc. Claustrophobia

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: single-blinded, monocentric, prospective crossover study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Intranasal placebo administration | Other: Placebo<br>* placebo intranasal administration<br>|
| Active Comparator: Intranasal insulin<br>Intranasal insulin administration | Other: intranasal insulin<br>* intranasal administration of insulin (160 IU)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of nasal insulin vs. placebo on the insulin sensitivity of the human brain as well as effects on regional availability of dopamine receptors. | assessed by fMRI (insulin sensitivity of the brain measured as change in regional brain activity and Raclopride-PET/MRT (regional dopamine receptor availability). | 0-60 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences between normalweight and overweight subjects regarding insulin sensitivity and availability of dopamine receptors | assessed by fMRI and Raclopride-PET/MRT | 0 - 60 min | 
| Effects of nasal insulin vs. placebo on changes in plasma insulin levels | assessed by blood sampling after application. | 0 - 60min | 
| Effects of nasal insulin vs. placebo on changes in plasma glucose levels | assessed by blood sampling after application. | 0 - 60min | 
| Effects of nasal insulin vs. placebo on changes in FFA levels | assessed by blood sampling after application. | 0 - 60min | 
| Effects of nasal insulin vs. placebo on changes in prolactin levels as a proxy for the dopaminergic tonus | assessed by blood sampling after application. | 0 - 60min | 
| Effects of nasal insulin vs. placebo on changes in autonomic nervous system | assessed by heart rate variability. | -30 - 60 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes mellitus, Type 2, cerebral insulin resistance, insulin action in the human brain, dopamine signalling