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Enhancing Brain Health by TDCS in Persons with Overweight and Obesity

Not Applicable
Active, not recruiting
Conditions
Obesity
Insulin Resistance
Diabetes Type 2
Interventions
Device: anodal transcranial direct current stimulation
Device: sham transcranial direct current stimulation
Device: cathodal transcranial direct current stimulation
Registration Number
NCT05228067
Lead Sponsor
University Hospital Tuebingen
Brief Summary

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.

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Anodal stimulationanodal transcranial direct current stimulationAnodal tDCS of the hypothalamus network
Sham stimulationsham transcranial direct current stimulationSham tDCS of the hypothalamus network
Cathodal stimulationcathodal transcranial direct current stimulationCathodal tDCS of the hypothalamus network
Primary Outcome Measures
NameTimeMethod
Change in dopamine-dependent cognitive function20 minutes after tDCS stimulation

Changes in dopamine-dependent cognitive function and reward sensitivity measured by a reward-based decision-making task

Change in neuroplasticity20 minutes directly before and after tDCS stimulation

Fractional anisotropy (FA) of the target network

Change in eating behavior1 hour after tDCS stimulation

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

Change in functional connectivity20 minutes directly before and after tDCS stimulation

Resting state functional connectivity of the target network

Secondary Outcome Measures
NameTimeMethod
Food choicetask is performed immediately after buffet

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 \[Scale: 1= not tasty/ not healthy up to 5= very tasty/ very healthy\]

Performance during stop-signal tasktask is performed during 25-minutes tDCS stimulation

Outcome measures cover direction errors, proportion of successful stops, reaction time on Go trials, and stop signal reaction time (SSRT)

Change in subjective ratings5 minutes before tDCS stimulation, 5 minutes after tDCS stimulation and 5 minutes after buffet

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

Tastiness and healthiness rating of food stimulitask is performed immediately after buffet

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

Trial Locations

Locations (1)

University Clinic Tübingen

🇩🇪

Tübingen, Germany

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