Transport of Satiety Factors Into the CSF

NCT04038086 | Unknown

• 1 other identifier: 397/2019BO1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Transport of proglucagon cleavage products into the CSF

  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

  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

  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

  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

  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 Outcomes (3)

• Association with hunger/satiety

  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

  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

  fasting state (0 minutes) and last CSF collection (120 minutes in Arm 1, 18 hours in Arm 2, and 240 minutes in Arm 3)

Study Arms (3)

oral glucose tolerance test

EXPERIMENTAL

Diagnostic Test: oral glucose tolerance test

circadian rhythm

OTHER

Other: circadian rhythm

effect of insulin on peptide transport

EXPERIMENTAL

Drug: effect of insulin on peptide transport

Interventions

oral glucose tolerance test DIAGNOSTIC_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.

oral glucose tolerance test

circadian rhythm OTHER

Blood and CSF will be collected five times throughout the day.

circadian rhythm

effect of insulin on peptide transport DRUG

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.

effect of insulin on peptide transport

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with cerebrospinal fluid drainage

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University of Tuebingen, Department of Internal Medicine IV

Tübingen, 72076, Germany

RECRUITING

MeSH Terms

Conditions

Obesity

Interventions

Glucose Tolerance Test; Circadian Rhythm

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Periodicity; Chronobiology Phenomena; Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2019
• First Posted: July 30, 2019
• Study Start: July 15, 2019
• Primary Completion: December 31, 2022
• Study Completion: June 1, 2023
• Last Updated: March 28, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)