Transport of Satiety Factors Into the CSF

Transport Von Peripheren Sättigungshormonen in Das Zentrale Nervensystem

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Diagnostic test: oral glucose tolerance test; Other: circadian rhythm; Drug: effect of insulin on peptide transport

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • Recruiting
    • University of Tuebingen, Department of Internal Medicine IV
    • Contact: Martin Heni, MD; Phone Number: +49 7071 29 82714; Email: martin.heni@med.uni-tuebingen.de
    • Principal Investigator: Martin Heni, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral glucose tolerance test	Diagnostic test: oral glucose tolerance test; 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.
Other: circadian rhythm	Other: circadian rhythm; Blood and CSF will be collected five times throughout the day.
Experimental: effect of insulin on peptide transport	Drug: effect of insulin on peptide transport; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association with hunger/satiety	Association of the measured peptides with hunger/satiety ratings (assessed on a visual analog scale) will be tested.	fasting state (0 minutes) and last CSF collection (120 minutes in Arm 1, 18 hours in Arm 2, and 240 minutes in Arm 3)
Association with depression-like behaviour	Association of the measured peptides with depression-like behaviour will be tested. Depression-like behaviour will be assessed by the BDI-II (Beck Depression Inventory) questionaire.	fasting state (0 minutes) and last CSF collection (120 minutes in Arm 1, 18 hours in Arm 2, and 240 minutes in Arm 3)
Association with mood	Association of the measured peptides with mood will be tested. Mood will be assessed by PANAS (Positive and Negative Affect Schedule) questionaire.	fasting state (0 minutes) and last CSF collection (120 minutes in Arm 1, 18 hours in Arm 2, and 240 minutes in Arm 3)

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: July 15, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 28, 2022
• Last Update Submitted That Met QC Criteria: March 25, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 397/2019BO1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We will not be able to share patient level data due to data protection regulations.

Drug and device information, study documents

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