About this trial
People with excess weight (EW) are characterized by high impulsivity, high levels of craving for high-calorie foods, deficits in inhibitory control, and maladaptive decision-making. These characteristics are related, at the brain level, to alterations in the activation of areas such as the dorsolateral prefrontal cortex (DLPFC) and its connectivity. The proposed intervention seeks to target these issues. Thus, the present study aims to characterize the effects of neuromodulation with intermittent theta burst transcranial magnetic stimulation (iTBS) of the DLPFC alone and in combination with inhibitory control training to produce brain, cognitive and behavioral changes, and modify altered biological parameters in people with EW. Participants will be randomly allocated to one of three groups: (1) a group that will receive active iTBS of the DLPFC combined with inhibitory control training with a food Go/No-go paradigm, (2) a group that will receive active iTBS of the DLPFC only, and (3) a control group that will receive sham iTBS. It is hypothesized that the combined intervention will obtain better results that the neuromodulation alone, and that both interventions, compared to sham iTBS, will achieve: (i) decreased body mass index, (ii) decreased craving, (iii) modified brain connectivity and activation both at rest and linked to task performance with food stimuli, (iv) improved anthropometric measures (waist circumference and waist-to-hip and waist-to-height ratios), (v) improved eating and exercise behaviors (decreased caloric intake and increased frequency and time of physical activity), (vi) improved emotional symptoms and emotional eating (depression, anxiety, emotional regulation, emotional eating, reward-related eating, non-homeostatic eating), (vii) improved cognitive abilities (motor and cognitive inhibition, delay of gratification, impulsivity, working memory, cognitive flexibility and decision making), (viii) changes in biological parameters associated to the interventions (plasma and microbiota), and (ix) advantages in cost-effectiveness and cost-utility based on economic evaluation analyses.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
BMI between 25 and 39.9
Age between 18 and 60 years
Proficiency in the Spanish language
Right lateral dominance to avoid differential effects due to cortical hemispheric specialization
Disqualifiers
Traumatic, digestive, metabolic or systemic disorders that affect the central nervous system, autonomic or endocrine
Severe psychopathological disorders and suicidal ideation or treatment for depression
Eating disorders
Contraindication for performing fMRI (pregnancy, metal implants, etc.) or iTBS (tinnitus, dizziness, surgical interventions, diseases or drugs that affect the CNS, etc.)
Trial design
Parallel
Treatments tested in this trial
iTBS of the left DLPFC
DeviceParticipants will receive a 3 minutes active theta burst transcranial magnetic stimulation (iTBS) of the DLPFC of the left hemisphere while not performing any other task
iTBS of the vertex
DeviceParticipants will receive a 3 minutes active theta burst transcranial magnetic stimulation (iTBS) of the vertex while not performing any other task
Inhibitory control training
BehavioralComputerized cognitive training. Participants will perform the task of the FoodT app for 10 minutes during two weeks (taking advantage of time of maximum brain potentiation after the iTBS, Rossi et al., 2009). Images of food and non-food appear on the left, right or centre of the smart phone screen and participants must touch it (or not, depending on the cue) with their index finger as quickly as possible. Participants earn points for correct tap responses and lose points for incorrect tap responses. If the image has a green border around it, participants must tap the image and win 1 point. But if the image has a red border around it, participants must inhibit the tapping response, otherwise 1 point will be lost. Participants must respond as quickly and accurately as possible. Pictures of healthy and unhealthy foods are always paired with the Go and the No-Go signal, respectively. Non-food images are paired 50% of the time with the Go and the No-Go signal
Treatment groups
Trial outcomes
Primary outcomes
Body Mass Index (BMI)
Change in BMI: Weight and height will be combined to report BMI in kg/m\^2. Weight will be obtained in kilograms with a digital scale (TANITA Corporation of America) and height in meters with a measuring rod (SECA Tape Measure 206).
Changes in brain activation during a inhibitory control task (neuroimaging measures)
Food Go/No-go task (Based on the FoodTrainer App; Lawrence et al., 2015): Pictures appear and afterwards a green (Go signal) or red (No-Go signal) circle appears around them. Participants are instructed to score points by answering with a knob if the image is surrounded by a green circle, but not to press when the image is surrounded by a red circle. The presentation of the images is the same as in the FoodTrainer application: 50% of the images are food, with 100% of the healthy ones being presented under the 'Go' condition and 100% of the unhealthy ones under the 'No-Go' condition. The remaining 50% are non-food images, with 50-50% paired with 'Go' and 'No-Go' cues. In addition, participants can choose which categories of unhealthy foods they want to train. Brain activation to Go vs. No-Go stimuli and food vs. non-food stimuli will be compared. The task will be analysed to assess the brain activity associated with the task, using a psychophysiological interaction analysis(PPI).
Secondary outcomes
Changes in Food decision-making (neuroimaging measures)
The Neveu et al. (2018) task will be used, which consists of three phases: two rating phases and one decision phase with 50 food images. Participants have to answer on a 5-point Likert scale how healthy they consider the food to be (block 1) and how much they like the taste of the food (block 2). In the third block, the participant decides whether they prefer to eat a neutral reference food (calculated from the previous two blocks) or an alternative food. These forced choices lead to cognitive conflict when the reference food is considered tastier and the alternative food healthier or vice versa. Among trials with cognitive conflict, the choice of the healthier food is defined as a controlled choice, and the choice of the tastier food as an uncontrolled choice. Activation will be compared between the controlled vs. uncontrolled choice conditions. The task will be analysed to assess the brain activity associated with the task, using a psychophysiological interaction analyses (PPI).
Changes in Brain connectivity at rest (neuroimaging measures)
Participants will be instructed to remain still, with their eyes closed, trying not to think about anything in particular for 9 minutes to obtain images to study the resting connectivity of different brain networks. On the one hand, an independent component analyses (ICA) will be performed, which will allow comparison of the different brain networks, as a whole, between the groups, with special interest in those that have been shown to be altered in the PD population. On the other hand, seed-based connectivity analyses will be performed, in which changes in functional connectivity between the CPFDL and the rest of the brain will be observed.
Changes in White matter integrity (neuroimaging measures)
Participants will be asked to remain still for 10 minutes to obtain diffusion tensor imaging (DTI) which provides indirect measurements of the architecture and connectivity of white matter fibres. The study of the DTI images will be carried out with the FSL programme, which allows the integrity of the white matter of the different groups to be measured by evaluating the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps.
Waist-to-height ratio (WHtR). Mean change from baseline at post-intervention
To take these measurements at home, participants should ask someone for help and follow our instructions. WHtR results from WC divided by the height measured standing with heels close together and trunk erect.
Other outcomes
Descriptive measures
A socio-demographic questionnaire will be administered to examine age, education, gender, socio-economic variables and clinical variables to consider exclusion and inclusion criteria. All these variables are qualitative.
Depression Symptoms. Screening
The Beck Depression Inventory (BDI-II) will also be used to rule out major depressive symptoms as an exclusion criteria. The scores range from 0 to 63 points. Participants with a score higher than 29, indicative of severe symptoms, will be excluded.
Anxiety Symptoms. Screening
The anxiety subscale of the DASS-21 will also be used to rule out symptoms of major anxiety as an exclusion criterion. The scores for both subscales range from 0 to 21. Participants with a score higher than 8, indicative of severe symptoms, will be excluded from the study.
Eating and Weight Patterns. Screening
Questionnaire on Eating and Weight Patterns-5 (QEWP-5) is adapted to DSM-5 criteria and will be used to exclude people with binge eating problems and bulimia. The QEWP-5 is not scored on a traditional numerical scale like other psychological tests; instead, responses are used to identify the presence of eating disorder symptoms. Positive responses to key questions about the frequency of binge eating, compensatory behaviors, and emotional distress may indicate the presence of an eating disorder.
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Raquel Vilar López
Lead sponsor
Universidad de Granada
Sponsor institution
Government of Spain
Collaborator