Enhancing Brain Health by TDCS in Persons with Overweight and Obesity (STIM)

Enhancing Brain Health to Prevent Type 2 Diabetes

Disturbances in the hypothalamus communication pathways with other regions in the brain and the periphery may represent a potential link between metabolic and cognitive health. The current project evaluates whether enhancing synaptic plasticity of this pathway can improve weight management, insulin sensitivity, and cognitive functions. In recent studies, we were able to show that the human brain is sensitive to insulin with favorable effects on peripheral metabolism and cognition. These brain regions encompass the hypothalamus and its connections to the striatum and prefrontal cortex. We want to investigate whether it is possible to enhance neuroplasticity of insulin-responsive brain regions to suppress the weight gain trajectory and improve dopamine-dependent cognitive functions in people with a high risk to develop type 2 diabetes. For this purpose, neuroimaging tools using high-definition transcranial direct current stimulation (HD-tDCS) and magnetic resonance imaging (MRI) will be implemented to assess synaptic plasticity of a neural network essential for metabolic and cognitive health.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Insulin Resistance; Diabetes Type 2
• Intervention / Treatment: Device: anodal transcranial direct current stimulation; Device: cathodal transcranial direct current stimulation; Device: sham transcranial direct current stimulation

Detailed Description

The overarching aim of the study is to investigate the possibility to enhance neuroplasticity of the hypothalamus network to improve metabolism and dopamine-dependent cognitive functions.

Specific objectives

• Specifically, it is the first aim to study the predictive value of white matter microstructure (fiber tracts structurally connecting the target network) for tDCS-intervention response and to investigate tDCS-induced neuroplasticity changes of the hypothalamus brain network using functional magnetic resonance imaging (fMRI).
• It is the second aim of this study to deepen our understanding of brain structure and function of the target network, which is known to rely on the neurotransmitter dopamine for its communication. Hence, we will use dopamine-dependent cognitive and eating behavior assessments.

Participants will receive a thorough screening to obtain body composition by MRI, anthropometric measures, fasting glucose and insulin, indirect calorimetry, and general cognitive functions. Thereafter, participants will participate in three measurement days (separated by approx. one week) to receive a 25 min tDCS stimulation targeting the hypothalamus network in a double-blind cluster-randomized. Participant are randomized on three conditions: sham stimulation, anodal and cathodal stimulation. During the non-invasive brain stimulation, participants will perform a stop-signal task. On each measurement day, structural and functional MRI measurements are performed before and after stimulation. Dopamine-dependent behavior (i.e. reward task) will be assessed during fMRI measurement. 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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• 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 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Written consent to participate in the study
• Written consent to be informed about incidental findings

Overweight and obese participants:

• Body mass index (BMI) between 28 and 39.5 kg/m2
• Age between 20 to 65 years of age
• Waist circumference > 80 cm for women, > 94 cm for men

Sex and age matched normal weight individuals:

• Body mass index (BMI) between 19.5 and 24.5 kg/m2
• Age between 20 to 65 years of age

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: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anodal stimulation; Anodal tDCS of the hypothalamus network	Device: anodal transcranial direct current stimulation; anodal tDCS of the hypothalamus resting-state functional connectivity network using 12 Electrodes of the Starstim device by Neuroelectrics. The total injected current will never go beyond 4 milliamp, which will be split among the different stimulation electrodes.; Other Names: anodal tDCS; excitatory tDCS
Active Comparator: Cathodal stimulation; Cathodal tDCS of the hypothalamus network	Device: cathodal transcranial direct current stimulation; anodal tDCS of the hypothalamus resting-state functional connectivity network using 12 Electrodes of the Starstim device by Neuroelectrics. The total injected current will never go beyond 4 milliamp, which will be split among the different stimulation electrodes.; Other Names: cathodal tDCS; inhibitory tDCS
Sham Comparator: Sham stimulation; Sham tDCS of the hypothalamus network	Device: sham transcranial direct current stimulation; Double blind sham stimulation of the hypothalamus resting-state functional connectivity network (ramp-up ramp-down stimulation will be applied for 30 seconds); Other Names: sham tDCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in eating behavior	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 after tDCS stimulation
Change in dopamine-dependent cognitive function	Changes in dopamine-dependent cognitive function and reward sensitivity measured by a reward-based decision-making task	20 minutes after tDCS stimulation
Change in neuroplasticity	Fractional anisotropy (FA) of the target network	20 minutes directly before and after tDCS stimulation
Change in functional connectivity	Resting state functional connectivity of the target network	20 minutes directly before and after tDCS stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in subjective ratings	Change in subjective ratings will be assessed using a visual analogue scale for hunger and subjective feeling of craving using a questionnaire (Food craving questionnaire). Visual analogue scale using a range from 0 to 10 cm, higher values indicating more hunger. Food craving questionnaire based on ordinal scale from 1 to 5, higher values indicating more food craving	5 minutes before tDCS stimulation, 5 minutes after tDCS stimulation and 5 minutes after buffet
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
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 immediately 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 healthy]	task is performed immediately after buffet

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2021
• Primary Completion (Actual): December 30, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: MRI; tDCS; functional connectivity; hypothalamus
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperinsulinism; Overweight; Obesity; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: 172/2021BO1

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
• product manufactured in and exported from the U.S.: No