Noninvasive Neuromodulation of the Prefrontal Cortex in Subjects With Obesity

Study Overview
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Brief Summary
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The overall goal of this proposal is to evaluate the efficacy of transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique, to facilitate weight loss and weight loss maintenance in obesity. This is a novel clinical research study that examines the therapeutic potential of an innovative biomedical treatment for weight loss.

Detailed Description
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The hypothesis is that tDCS will successfully engage prefrontal-related neurobehavioral cognitive control systems, resulting in decreased eating disinhibition and therefore facilitation of weight loss and weight loss maintenance. To test this hypothesis, a 6-month randomized, sham-controlled, double-blind, intervention study was designed. Subjects will undergo an intervention with the following components/phases: Phase 1 - Target engagement (one session) The purpose of this phase is to examine whether tDCS can reach the brain target, the dorsolateral prefrontal cortex, and influence performance in a neuropsychology tests that depends on the activity of this region. Results from this component of the study will provide evidence for target engagement. Genomic DNA will be extracted from whole blood for sequencing of Catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) polymorphism genotypes. Phase 2 - tDCS alone (two weeks) During this phase participants will receive daily tDCS sessions over the course of two weeks (Monday to Friday; total=10 sessions). The purpose of this phase is to examine the effect of modulating the activity of the prefrontal cortex with tDCS on body weight under baseline/weight stable conditions. Also analyse changes in appetite and eating behavior. Phase 3 - tDCS plus hypocaloric diet (two weeks). During this phase participants will undergo a hypocaloric diet intervention aimed at achieving a 5% body weight reduction at 3 months. The diet will be individualized on the basis of physical activity levels, age for each participant. This intervention will be be conducted at an inpatient, well-controlled setting to guarantee adherence to the diet. Here the diet intervention will be administered in combination with tDCS. tDCS will be applied every other day (Monday, Wednesday, Friday) over the course of these two weeks. The purpose of this component is to examine acute changes in weight associated with tDCS in combination with the diet. Also analyse changes in appetite and eating behavior. Phase 4 - Follow up (6 months). During this phase (outpatient) changes in body weight over time will be assessed to evaluate weight maintenance. Subjects will be asked to come back to the laboratory at 1, 3 and 6 months. Also analyse changes in appetite and eating behavior.

Official Title
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Noninvasive Neuromodulation of the Prefrontal Cortex in Subjects With Obesity: a Proof-of-concept Study

Conditions
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Obesity

Intervention / Treatment
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* Device: Active transcranial direct current stimulation (tDCS)
* Other: Hypocaloric diet
* Other: Sham transcranial direct current stimulation (tDCS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with obesity (BMI 30-35 kg/m2), with stable weight over the previous 3 months. Exclusion Criteria: pregnancy diabetes acute and chronic kidney disease pancreatitis any active psychiatric or neurological condition at the time of joining the study intake of centrally-acting medications that could interfere with tDCS effects anemia (Hgb <12 g/dl) any other significant medical condition contraindications for tDCS, which includes damaged skin at the site of stimulation, any electrically sensitive or metallic device and history of epilepsy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active group<br>Active transcranial direct current stimulation (tDCS) and hypocaloric diet. | Device: Active transcranial direct current stimulation (tDCS)<br>* Participants will receive 10 daily sessions (phase 2) and 3 times a week (phase 3) of tDCS (2mA, 30 min per session). The tDCS montage will target the left dorsolateral prefrontal cortex (DLPFC) (anode: F3 based on the 10:20 system; cathode over the right supraorbital area). For stimulation the investigators will use 5x5cm sponge pads that will be soaked in 0.9% saline during the sessions.<br>Other: Hypocaloric diet<br>* During phase 3, participants will undergo a supervised hypocaloric diet intervention for 2 weeks based on a low-calorie diet (LCD) providing a hypocaloric diet based in 20% reduction from total energy expenditure (TEE). The diet will be individualized on the basis of physical activity levels, age for each participant. This intervention will be be conducted at an inpatient, well-controlled setting to guarantee adherence to the diet. Here the diet intervention will be administered in combination with tDCS. tDCS will be applied every other day (Monday, Wednesday, Friday) over the course of these two weeks.<br>|
| Sham Comparator: Control group<br>Sham transcranial direct current stimulation (tDCS) and hypocaloric diet. | Other: Hypocaloric diet<br>* During phase 3, participants will undergo a supervised hypocaloric diet intervention for 2 weeks based on a low-calorie diet (LCD) providing a hypocaloric diet based in 20% reduction from total energy expenditure (TEE). The diet will be individualized on the basis of physical activity levels, age for each participant. This intervention will be be conducted at an inpatient, well-controlled setting to guarantee adherence to the diet. Here the diet intervention will be administered in combination with tDCS. tDCS will be applied every other day (Monday, Wednesday, Friday) over the course of these two weeks.<br>Other: Sham transcranial direct current stimulation (tDCS)<br>* Subjects in the control group will receive sham stimulation (placebo) (similar procedure and duration as real tDCS, but here electric current flows for 30 s only, to mimic the subjective sensations that occur with active tDCS).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight | The primary outcome will be change in body weight after two weeks intervention (tDCS alone) versus baseline (day 1), the change in body weight between the beginning and the end of the inpatient period (tDCS plus hypocaloric diet), and the change in body weight throughout follow-up (6 months), i.e. between the end of the tDCS intervention (end of the inpatient phase) and the end of the study. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Appetite visual analogue scale | The investigators will analyse changes in appetite during the different phases of the study: phase 1 (target engagement), phase 2 (tDCS-only effect), phase 3 (tDCS plus diet effect), phase 4 (follow-up) using the visual analogue scale. | 6 months | 
| Eating behavior questionnaire | The investigators will analyse changes in eating behavior during the different phases of the study: phase 1 (target engagement), phase 2 (tDCS-only effect), phase 3 (tDCS plus diet effect), phase 4 (follow-up) using the three-factor eating and food craving questionnaires. | 6 months | 
| Cognitive performance in a food modified working memory test | The investigators will compare accuracy and reaction times before and after the 2 weeks with tDCS only. To evaluate working memory performance an N-back task will be used. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Feeding behavior, Transcranial direct current stimulation, Weight loss