Clinical trial NCT02870361: Influence of Central Nervous Insulin Sensitivity on Insulin Secretion
Official title: Einfluss Der zentralnervösen Insulinsensitivität Auf Die Insulinsekretion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Secretion
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2016-08-17
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Insulin resistance is a central pathophysiological component of type 2 diabetes and is associated with a high risk of cardiovascular disease. The tissue in which it manifests are mainly muscle, liver, and adipose tissue. Since the transport of glucose to the brain is independent of insulin, this organ has traditionally not been studied in this regard. In animal experiments, however, knockout of the insulin receptor in the brain leads to obesity and peripheral insulin resistance. This finding of insulin action in the brain could also be confirmed in human studies.

The investigators intend to investigate whether central nervous insulin action affects insulin secretion in humans. For this purpose, nasal insulin and placebo are administered 15 minutes before a hyperglycemic hyperinsulinemic clamps, which stimulate insulin secretion. Insulin sensitivity of the brain is measured by a an established protocol with functional magnetic resonance imaging before and after nasal insulin administration.


Eligibility criteria: Inclusion Criteria:

* HbA1c ≤6.0%
* normal glucose tolerance during 75g oral glucose tolerance test (OGTT)

Exclusion Criteria:

* Not removable metal parts in or on the body
* manifest cardiovascular disease
* claustrophobia
* recent surgery (less than 3 months)
* Simultaneous participation in other studies
* Acute disease or infection within the last 4 weeks
* neurological and psychiatric disorders
* treatment with centrally acting drugs
* hemoglobin Hb \<13g / dl
* Hypersensitivity to any of the substances used

Primary outcomes:
measure: Insulin secretion assessed as serum C-peptide levels during a hyperglycemic clamp
timeFrame: 0-10 min during hyperglycemic clamp and 10-90 min during hyperglycemic clamp
Secondary outcomes:
measure: Correlation with brain insulin sensitivity
timeFrame: 15-30 minutes post insulin nasal spray
measure: Differential effects in lean and overweight
timeFrame: 0-10 min during hyperglycemic clamp and 10-90 min during hyperglycemic clamp
measure: Correlation with autonomous nervous system activity
timeFrame: 10 - 150 minutes post nasal spray
measure: Peripheral insulin sensitivity
timeFrame: 10-90 min and 70-90 min during hyperglycemic clamp
Other outcomes:
Locations:
city: Tübingen
country: Germany
facility: University of Tuebingen, Department of Internal Medicine IV
Study officials:
affiliation: University Hospital Tuebingen
name: Martin Heni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heni M, Wagner R, Willmann C, Jaghutriz BA, Vosseler A, Kubler C, Hund V, Scheffler K, Peter A, Haring HU, Preissl H, Kullmann S, Fritsche A. Insulin Action in the Hypothalamus Increases Second-Phase Insulin Secretion in Humans. Neuroendocrinology. 2020;110(11-12):929-937. doi: 10.1159/000504551. Epub 2019 Nov 5.