Pupillography as Screening Tool for Brain Insulin Resistance

Study Overview
=================
Brief Summary
-----------------
Cerebral insulin action is important in the regulation of whole body glucose metabolism. However, the cerebral insulin action differs between individuals - there is a so called cerebral insulin resistance. The influence of central insulin action on peripheral metabolism seems at least partially mediated via the autonomous nervous system. A noninvasive method to measure autonomic function is the pupillography. The aim of the study is to find out whether pupillography can be used to assess central insulin activity. Thus, pupillography will be performed in 30 normal weight and 30 overweight subjects before and after application insulin intranasally.

Official Title
-----------------
Pupillographie Als Screeningtest für Cerebrale Insulinresistenz

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Drug: human insulin
* Drug: placebo
* Diagnostic Test: Pupillography


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: voluntary adults HbA1c <5.8% Age between 18 and 60 years written consent Exclusion Criteria: There is a pregnancy or pregnancy can not be excluded lactating women Minors or non-consenting subjects are also excluded Acute illness or infection within the last 4 weeks Neurological and psychiatric disorders intake of centrally acting drugs Subjects with hemoglobin levels Hb <12g / dl (in females), Hb <14g / dl (males) Allergic diseases against one of the substances used

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: nasal insulin<br>160 U of human insulin as nasal spray | Drug: human insulin<br>* human insulin administered as nasal spray<br>Diagnostic Test: Pupillography<br>* Autonomic tone will be adressed by pupillography using the F2D2 (Amtech Germany) device.<br>|
| Placebo Comparator: nasal placebo<br>placebo as nasal spray | Drug: placebo<br>* placebo administered as nasal spray<br>Diagnostic Test: Pupillography<br>* Autonomic tone will be adressed by pupillography using the F2D2 (Amtech Germany) device.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurements of autonomic nervous system activity by pupillography | There will be measurements of autonomic nervous system activity by pupillography in order to identify central insulin action. The primary variable is the pupil width change in pupillography before compared to after intranasal insulin/placebo administration in 30 lean subjects. The investigation takes place in a darkened room with low backlight of about 5-10lx. The pupillographic recording is carried out with a commercially available device, F2D2 (Amtech Germany). In this case, the pupil width is recorded for 6 minutes continuously before and after nasal insulin (also 16 strokes of 10 E) or placebo doses with an infrared camera permanently mounted in a video goggle. Additionally, a possible change of the pupillary light reflection to monochromatic light is measured. Evaluation parameters are latency, amplitude and re-dilatation behavior. | Measurements baseline and change to baseline 15 minutes and 30 minutes after spray application | 
| Measurements of latency of pupil response to light stimulation. | There will be measurements of autonomic nervous system activity by pupillography in order to identify central insulin action. The investigation takes place in a darkened room with low backlight of about 5-10lx. The pupillographic recording is carried out with a commercially available device, F2D2 (Amtech Germany). A possible change of the pupillary light reflection to monochromatic light is measured. Evaluation parameter is latency. The responses before and after nasal spray administration will be compared. | Measurements baseline and change to baseline 15 minutes and 30 minutes after spray application | 
| Measurements of amplitude of pupil response to light stimulation. | There will be measurements of autonomic nervous system activity by pupillography in order to identify central insulin action. The investigation takes place in a darkened room with low backlight of about 5-10lx. The pupillographic recording is carried out with a commercially available device, F2D2 (Amtech Germany). A possible change of the pupillary light reflection to monochromatic light is measured. Evaluation parameter is amplitude . The responses before and after nasal spray administration will be compared. | Measurements baseline and change to baseline 15 minutes and 30 minutes after spray application | 
| Measurements of re-dilation behaviour of pupil response to light stimulation. | There will be measurements of autonomic nervous system activity by pupillography in order to identify central insulin action. The investigation takes place in a darkened room with low backlight of about 5-10lx. The pupillographic recording is carried out with a commercially available device, F2D2 (Amtech Germany). A possible change of the pupillary light reflection to monochromatic light is measured. Evaluation parameter is re-dilatation behavior. The responses before and after nasal spray administration will be compared. | Measurements baseline and change to baseline 15 minutes and 30 minutes after spray application | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Autonomic nervous system | effect of nasal insulin or placebo spray on autonomic nervous system tone measured by heart rate variability. | Measurements baseline and change to baseline 15 minutes and 30 minutes after spray application |