Clinical trial NCT05228067: Enhancing Brain Health by TDCS in Persons with Overweight and Obesity
Official title: Enhancing Brain Health to Prevent Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Insulin Resistance
Obesity
Diabetes Type 2
Keywords: tDCS
MRI
hypothalamus
functional connectivity
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2022-02-08
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: All participants receive sham stimulation, anodal stimulation and cathodal stimulation in a pseudo-randomized order on three separate measurement days.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in neuroplasticity
timeFrame: 20 minutes directly before and after tDCS stimulation
measure: Change in functional connectivity
timeFrame: 20 minutes directly before and after tDCS stimulation
measure: Change in eating behavior
timeFrame: 1 hour after tDCS stimulation
measure: Change in dopamine-dependent cognitive function
timeFrame: 20 minutes after tDCS stimulation
Secondary outcomes:
measure: Change in subjective ratings
timeFrame: 5 minutes before tDCS stimulation, 5 minutes after tDCS stimulation and 5 minutes after buffet
measure: Performance during stop-signal task
timeFrame: task is performed during 25-minutes tDCS stimulation
measure: Tastiness and healthiness rating of food stimuli
timeFrame: task is performed immediately after buffet
measure: Food choice
timeFrame: task is performed immediately after buffet
Other outcomes:
Locations:
city: Tübingen
country: Germany
facility: University Clinic Tübingen
Study officials:
References: