Pupillography as Screening Tool for Brain Insulin Resistance

Pupillographie Als Screeningtest für Cerebrale Insulinresistenz

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: human insulin; Diagnostic test: Pupillography; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • University of Tuebingen, Department of Internal Medicine IV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: nasal insulin; 160 U of human insulin as nasal spray	Drug: human insulin; human insulin administered as nasal spray; Diagnostic test: Pupillography; Autonomic tone will be adressed by pupillography using the F2D2 (Amtech Germany) device.
PLACEBO_COMPARATOR: nasal placebo; placebo as nasal spray	Diagnostic test: Pupillography; Autonomic tone will be adressed by pupillography using the F2D2 (Amtech Germany) device.; Drug: placebo; placebo administered as nasal spray

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

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 3, 2018
• Primary Completion (ACTUAL): November 1, 2018
• Study Completion (ACTUAL): January 7, 2019

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: August 27, 2018
• First Posted (ACTUAL): August 29, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 10, 2019
• Last Update Submitted That Met QC Criteria: January 9, 2019
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 567/20168O2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No