Transport of Satiety Factors Into the CSF

Study Overview
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Brief Summary
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The blood-brain barrier regulates the passage of peripheral built appetite-suppressing hormones from the blood to the brain and informs the brain about the nutritional- and energy status. The aim of this study is to investigate in which extent the hormones are able to overcome the blood-brain barrier and how long it takes after food intake. Relating thereto indications to the effect of peripheral hormones in the central nervous system and the role of these hormones in the development of overweight are provided. In this study 30 patients (10 per intervention group) will be recruited. The patients are hospitalized in the local neurosurgery and they have a CSF-drainage due to their neurological primary disease or due to neurosurgical interventions. The patients are examined in each case on the same day. Simultaneous samplings of blood and CSF are taken from 10 patients after an oral glucose tolerance test. These interventions are carried out to investigate in which extent the appetite-suppressing hormones (e.g. Leptin, Insulin, GLP 1 and Glucagon) reach the liquor and so the central nervous system. In order to understand the temporal sequence, simultaneous samplings of blood and CSF are taken from 10 other patients at certain points throughout the day. In a further group of 10 patients will be investigated how the central effective insulin modulates the transport of the other appetite-suppressing hormones. Therefore samplings of blood and CSF are investigated before and after intranasal insulin administration.

Official Title
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Transport Von Peripheren Sättigungshormonen in Das Zentrale Nervensystem

Conditions
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Obesity

Intervention / Treatment
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* Diagnostic Test: oral glucose tolerance test
* Other: circadian rhythm
* Drug: effect of insulin on peptide transport


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with cerebrospinal fluid drainage Exclusion Criteria: Women during pregnancy and lactation Participation in other interventional clinical trials severe infection within the last 4 months intake of central effective substances which may interact with the transport processes to be investigated hypersensitivity to any of the substances used diabetes mellitus Patients with CSF results indicative of infectious diseases within the central nervous system subjects with hemoglobin Hb <10 g / dl Patients with a neurosurgical disorder suspected of having a blood-brain barrier disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral glucose tolerance test<br> | Diagnostic Test: oral glucose tolerance test<br>* Participants will undergo an 75 gram oral glucose tolerance test. Blood and CSF will be collected in the fasting state before the test and every 30 minutes throughout the test which lasts for 2 hours.<br>|
| Other: circadian rhythm<br> | Other: circadian rhythm<br>* Blood and CSF will be collected five times throughout the day.<br>|
| Experimental: effect of insulin on peptide transport<br> | Drug: effect of insulin on peptide transport<br>* Blood and CSF will be collected in the fasting state and 15, 30, 60, 120 und 240 min after administration of 160 U of human insulin as nasal spray.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin transport into the CSF | Insulin will be measured in serum and CSF and the ratio will be calculated. | Sample collection will be from 0 to 120 minutes in Arm 1, 18 hours in Arm 2, and 0 to 240 minutes in Arm 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transport of proglucagon cleavage products into the CSF | Proglucagon cleavage products will be measured in serum and CSF and the ratio will be calculated. | Sample collection will be from 0 to 120 minutes in Arm 1, 18 hours in Arm 2, and 0 to 240 minutes in Arm 3 | 
| Transport of FGF21 and FGF23 into the CSF | FGF21 and FGF23 will be measured in serum and CSF and the ratio will be calculated. | Sample collection will be from 0 to 120 minutes in Arm 1, 18 hours in Arm 2, and 0 to 240 minutes in Arm 3 | 
| Ghrelin transport into the CSF | Ghrelin will be measured in serum and CSF and the ratio will be calculated. | Sample collection will be from 0 to 120 minutes in Arm 1, 18 hours in Arm 2, and 0 to 240 minutes in Arm 3 | 
| PYY transport into the CSF | PYY will be measured in serum and CSF and the ratio will be calculated. | Sample collection will be from 0 to 120 minutes in Arm 1, 18 hours in Arm 2, and 0 to 240 minutes in Arm 3 | 
| Leptin transport into the CSF | Leptin will be measured in serum and CSF and the ratio will be calculated. | Sample collection will be from 0 to 120 minutes in Arm 1, 18 hours in Arm 2, and 0 to 240 minutes in Arm 3 |