Improving Insulin Sensitivity by Non-invasive Brain Stimulation

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. In recent studies, the hypothalamus was identified as 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. In this project, transcranial direct current stimulation (tDCS) is implemented as a tool to stimulate brain networks. 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.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes; Insulin Resistance; Magnetic Resonance Imaging; Transcranial Direct Current Stimulation
• Intervention / Treatment: Device: transcranial direct current stimulation

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

1. Implement tDCS stimulation compared to sham stimulation in overweight and obese adults to assess the impact on eating behavior, cognition and metabolism.
2. Evaluate whether 3-day non-invasive brain stimulation of the hypothalamus-cognitive network has a causal effect on metabolism.
3. Evaluate whether 3-day non-invasive brain stimulation has a significant effect on brain functional connectivity and diffusion parameters.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • University clinic Tübingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index (BMI) between 25.5 and 39.5 kg/m2
• Age between 20 to 66 years of age
• Waist circumference ≥ 80 cm for women, ≥ 94 cm for men

Exclusion Criteria:

• Insufficient knowledge of the German language
• Persons who cannot legally give consent
• Pregnancy or lactation
• History of severe mental or somatic disorders including neurological diseases (incl. epileptic seizures)
• Taking psychotropic drugs
• Previous bariatric surgery
• Acute infection within the last 4 weeks
• Hemoglobin values less than 12g/dl for women, less than 14 g/dl for men
• Current participation in a lifestyle intervention study or a pharmaceutical study
• Contradictions to a MRI measurement (e.g. metal implants)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anodal tDCS; Anodal tDCS of the hypothalamus-cognitive network	Device: transcranial direct current stimulation; anodal or cathodal transcranial direct current stimulation
Active Comparator: Cathodal tDCS; Cathodal tDCS of the hypothalamus-cognitive network	Device: transcranial direct current stimulation; anodal or cathodal transcranial direct current stimulation
Sham Comparator: Sham Stimulation; Double blind sham stimulation (ramp-up ramp-down stimulation will be applied in order to simulate the active condition without any further continuous administration of current)	Device: transcranial direct current stimulation; anodal or cathodal transcranial direct current stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral insulin sensitivity	Oral glucose tolerance derived insulin sensitivity based on the Matsuda index	1 day after last intervention tDCS day
Caloric intake (kcal)	Free-choice, ad libitum food intake from a standardized breakfast buffet. The caloric intake from fat, carbohydrates and protein will be documented.	1 hour directly after tDCS stimulation
Change in subjective feeling of hunger and food craving	On a visual analogue scale, subjective feeling of hunger and food craving will be assessed using a questionnaire.	5 minutes before tDCS stimulation, 5 minutes after tDCS stimulation and 5 minutes after buffet

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tastiness and healthiness rating of food stimuli	Using a computer based task, participants rate food pictures of low caloric and high caloric foods and snacks on a 5-point scale based on subjective tastiness and healthiness.	task is performed immediatly after buffet
Food choice	Using a computer based task, participants have to choose food items they preferred to eat compared to a reference food on a 5-point choice scale. The reference (or "neutral") food item is individually determined based the health and taste rating [Scale: 1= not tasty/ not healthy up to 5= very tasty/ very heahlty].	task is performed immediatly after buffet
Functional connectivity	Resting-state functional connectivity of the hypothalamus-cognitive network is assessed by functional magnetic resonance imaging (fMRI)	10 minutes functional MRI measurement performed before and after three day tDCS stimulation
Diffusion-weighted imaging	Diffusion weighted parameter based on MRI measurements	15 minutes MRI measurement performed before and after three day tDCS stimulation
Performance during stop-signal task	Outcome measures cover direction errors, proportion of successful stops, reaction time on Go trials, and stop signal reaction time (SSRT).	task is performed during 25-minutes tDCS stimulation

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: German Center for Diabetes Research
• Investigators: Principal Investigator: Stephanie Kullmann, PhD, Univeristy of Tübingen, Germany

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2020
• Primary Completion (Actual): October 31, 2023
• Study Completion (Actual): November 10, 2023

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: BRAINSTIM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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