NCT04052399

Improving Insulin Sensitivity by Non-invasive Brain Stimulation in Persons With Insulin Resistance

Improving Insulin Sensitivity by Non-invasive Brain Stimulation- Feasibility Study

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: University Hospital Tuebingen · Academic / Other
• Sex: All
• Age: 20 Years – 60 Years
• Healthy volunteers: Accepted

Summary

Efforts in curing and preventing obesity and type 2 diabetes (T2D) have been elusive thus far. One reason for that is the lack of understanding of the role of the brain in the development and treatment of the disease. Insulin action in the brain is appreciated to play a vital role in the pathophysiology of T2D, influencing eating behavior, cognition and peripheral metabolism. Whether brain insulin resistance is a cause or consequence of prediabetes is not yet fully understood. Hence, in this project the investigators want to develop a novel tool to treat and prevent type 2 diabetes and to delineate brain mechanisms of insulin resistance in humans. For this purpose, transcranial direct current stimulation (tDCS) will be implemented, which is a powerful tool to stimulate brain networks. In recent studies, it was shown that the hypothalamus is part of a brain network including higher cognitive regions that is particularly vulnerable to insulin resistance. Furthermore, the central insulin response in this network predicted food craving and hunger. The investigators hypothesize that stimulating the hypothalamus-cognitive network will enhance insulin sensitivity and reduce food intake, food craving and hunger. Furthermore, the project will provide the unique opportunity to investigate novel mechanisms of insulin resistance in participants who have been extensively metabolically characterized.

Detailed description

Objectives The overarching aim of the study is to stimulate the hypothalamus-cognitive brain network to improve insulin sensitivity and eating behavior. Specific Objectives- Feasibility study: 1. Implement resting-state functional magnetic resonance imaging to identify individual medial and lateral hypothalamic cognitive functional networks. 2. Evaluate and test different non-invasive brain stimulation paradigms by tDCS to stimulate lateral and medial hypothalamus cognitive network on eating behavior and metabolism. 20 participants with overweight and obesity will receive five different tDCS stimulation protocols on five separate days (separated by one week) in a single-blind cluster-randomized order to reduce sequence effects. Optimal stimulation sites are assessed of the lateral and medial hypothalamus-cognitive network based on a modelling approach. Since this is the first study to stimulate the hypothalamus-cognitive network, excitatory as well as inhibitory stimulation is used. To reduce the number of conditions, participant are randomized based on the three main conditions: sham stimulation, anodal and cathodal stimulation. Medial hypothalamus-cognitive network versus lateral hypothalamus-cognitive network stimulation are pseudo-randomised. Participants will come in the morning, after an overnight fast, to receive a 20 min non-invasive brain stimulation, using tDCS. During the stimulation, participants will perform a stop-signal task on an tablet. Subsequently, participants will receive a breakfast buffet. The caloric intake from fat, carbohydrates and protein will be documented. Subjective feeling of hunger and food craving will be assessed using a visual analogue scale before stimulation, directly after stimulation and after breakfast. Food pictures will be rated on a laptop for taste and healthiness.

Conditions

• Insulin Resistance
• Transcranial Direct Current Stimulation

Interventions

Type	Name	Description
DEVICE	anodal transcranial direct current stimulation	Anodal tDCS of the lateral hypothalamus-cognitive or medial hypothalamus-cognitive network. The total injected current will never go beyond 4 milliamp, which will be split among the different stimulation electrodes.
DEVICE	cathodal transcranial direct current stimulation	Cathodal tDCS of the lateral hypothalamus-cognitive or medial hypothalamus-cognitive network. The total injected current will never go beyond 4 milliamp, which will be split among the different stimulation electrodes.
DEVICE	transcranial direct current stimulation	Single blind sham stimulation (ramp-up ramp-down stimulation will be applied for 30 seconds)

Timeline

• Start date: 2019-11-04
• Primary completion: 2020-12-31
• Completion: 2021-12-31
• First posted: 2019-08-09
• Last updated: 2020-05-14

Locations

1 site across 1 country: Germany