Effects of Age and Obesity on Brain Insulin Sensitivity

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EstadoReclutamiento

Patrocinadores

University Hospital Tuebingen

ENSAYO CLÍNICO: NCT04372849

BioSeek: nct04372849

Palabras clave

Abstracto

Obesity and especially type 2 diabetes (T2D) increases the risk of neurocognitive dysfunctions including adverse effects on brain structure and function. Recent evidence from clinical studies have shown that T2D almost doubles the risk for dementia. As the population gets older, age-related chronic diseases, as T2D, become more prevalent. Scientific evidence is emerging that there are several links between metabolic and neurocognitive functions. Impaired insulin action (i.e. insulin resistance), the main hallmark of T2D, has been suggested as a likely shared common pathophysiological mechanism. However, the neural processes that determine how insulin resistance is are connected to the onset and progression of T2D and dementia remain unclear. In this context, the overall aim is to study brain insulin resistance to disentangle age-related and obesity related brain insulin resistance in healthy normal and overweight/obese persons at the age of 20 to 70 years . To this end, the investigators will assess brain insulin action using intranasal insulin/placebo during functional Magnetic Resonance Imaging (fMRI). Additionally, structural changes and cognitive processes will be assessed as secondary variables.

fechas

Verificado por última vez:	03/31/2020
Primero enviado:	04/28/2020
Inscripción estimada enviada:	04/28/2020
Publicado por primera vez:	05/03/2020
Última actualización enviada:	04/28/2020
Última actualización publicada:	05/03/2020
Fecha de inicio real del estudio:	04/27/2017
Fecha estimada de finalización primaria:	09/29/2020
Fecha estimada de finalización del estudio:	12/29/2020

Condición o enfermedad

Insulin Resistance

Obesity

Intervención / tratamiento

Other: Nasal insulin spray

Other: Placebo spray

Fase

Grupos de brazos

Brazo	Intervención / tratamiento
Active Comparator: Nasal insulin spray	Other: Nasal insulin spray single dose of 160 U of human insulin as nasal spray
Placebo Comparator: Placebo spray	Other: Placebo spray Single dose of placebo solution as nasal spray

Criterio de elegibilidad

Edades elegibles para estudiar	20 Years A 20 Years
Sexos elegibles para estudiar	All
Acepta voluntarios saludables	si
Criterios	Inclusion Criteria: - Body-Mass Index (BMI) between 19-35 kg/m2 - 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

Salir

Medidas de resultado primarias

1. Brain insulin sensitivity in different age,weight and sex groups [30 minutes after administration of nasal insulin]

fMRI measurement will be performed before and after administration of 160 U of human insulin or placebo as nasal spray. Changes in regional brain activity will be quantified by cerebral blood flow and blood oxygenation dependent (BOLD) signal to assess regional brain insulin sensitivity. Brain insulin sensitivity will be compared between eight groups (young normal weight men and women, young overweight/obese men and women, old normal weight men and women, old overweight/obese men and women). Persons are categorized into normal weight and overweight/obese based on the Body Mass Index (BMI). Age groups are build based on a median split.

Medidas de resultado secundarias

1. Whole-body insulin sensitivity [2 hours]

Insulin sensitivity will be estimated from a frequent-sampling 75 g oral glucose tolerance test (oGTT) using the Matsuda formula. Correlation of regional brain insulin sensitivity by intranasal insulin will be performed with whole-body insulin sensitivity based on oGTT. Changes in regional cerebral blood flow from before to after intranasal insulin administration will be assessed by functional magnetic resonance imaging (fMRI).

2. Correlation with autonomous nervous system activity [10 - 150 minutes post nasal spray]

Correlation of the change in regional brain insulin sensitivity by intranasal insulin with the simultaneous change of the autonomous nervous system (measured by heart rate variability).

3. Correlation with cognitive function [1 hours]

Correlation of the change in regional brain insulin sensitivity by intranasal insulin with cognitive measures addressed by neuropsychological testing.

4. Response to food cues [20 minutes]

Brain response to food cues assessed by functional magnetic resonance imaging. Food cues will be rated for palatability on a visual analogue scale.

Effects of Age and Obesity on Brain Insulin Sensitivity

Palabras clave

demencia

diabetes mellitus tipo 2

resistencia a la insulina

obesidad