Pilot Study of an Intervention Involving Cognitive Training and tDCS in Morbidly Obese Subjects

Study Overview
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Brief Summary
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The study aims to: 1) investigate the effects of cognitive training (CT) and combined CT and transcranial direct current stimulation (tDCS) on food intake and 2) to further understand its neuropsychological and neurophysiological basis (i.e. EEG) as well as its impact in endocannabinoids (EC) in a sample of morbidly obese patients seeking for a gastric bypass surgery

Detailed Description
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The study will explore the impact of a 4-day intervention with either CT (Active control condition) or CT+tDCS (Active condition) stimulation on food intake in a sample of morbidly obese patients, as measured by dietary assessments the week before, during and the week after the intervention. Additionally, to further understand the neuropsychological and neurophysiological basis of its impact, measures of executive function and attention performance and EEG recordings, respectively, will be collected. Furthermore, we will explore the effect of the intervention on endocannabinoids previously related to eating behaviour. The Active Control condition will receive sham stimulation together with CT, through a computerized cognitive training platform (Guttmann NeuropersonalTrainer), including different tasks with designed to train executive functions and attention. Each session will last approximately 30-40 min. The Active condition will receive tDCS stimulation (20 min, multichannel with an excitatory target over the r-dlPFC) together with CT (same as for the Active Control condition). Participants will undergo a basal (the week before intervention) and a post treatment assessments (the day after finishing the intervention) that will include medical history, blood testing, anthropometric measures, a cognitive assessment battery and a 4-day dietary assessment.

Official Title
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Pilot Study of an Intervention Involving Cognitive Training and Transcranial Direct-current Stimulation (tDCS) in Morbidly Obese Subjects

Conditions
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Obesity, Morbid, Obesity (BMI > 35) and Diabetes Mellitus, Obesity (BMI > 35) and High Blood Pressure, Obesity (BMI > 35) and Dyslipemia

Intervention / Treatment
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* Other: Cognitive Training
* Device: transcranial Direct-Current Stimulation (tDCS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects of both gender, aged between 18 and 60 years-old Having a BMI > 40 kg/m2 or having a BMI>35 and suffering from diabetes mellitus, HBP or LDP. Obesity conventional treatment failure Wish of bariatric surgery Accepting the study and signing the Informed Consent Exclusion Criteria: Do not meet inclusion criteria Being left-handed Using a pacemaker or deep cerebral stimulation device Having a psychiatric disease or serious disease Neurologic condition or learning issue or mental backwardness that could affect cognitive function Use of psycho-stimulating medicines and/or drugs, abuse or dependance to a psychoactive substance (or during the last 6 months) Dependance to alcohol or/and drugs (excepted from nicotina) In treatment with benzodiazepines, antipsychotics, tricyclic antidepressants or topiramate, started in the last month History of psychiatric disorders treated with lithio carbonate. Cutaneous lesion on the area of using of electrodes Contact allergy to material used in the used devices.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: Active Control group: Subjects will receive CT and sham tDCS during four consecutive days. Active group: Subjects will receive CT and active tDCS during four consecutive days.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Active Control group<br>This group will receive CT and sham tDCS each day, for four days. | Other: Cognitive Training<br>* Cognitive Training (CT): 4 consecutive days, 30-45 min session involving 5 different tasks designed to train executive functions and attention, available at the Guttmann Neuropersonaltrainer platform (computerized cognitive training tool certified by the Spanish Agency for Medicines and Health Products as a Class I Health Product). The difficulty level of all the tasks was automatically adjusted on a trial-by-trial basis for both Active and Active Control conditions.<br>|
| Active Comparator: Active group<br>This group will receive both CT and tDCS, each day, for four days. | Other: Cognitive Training<br>* Cognitive Training (CT): 4 consecutive days, 30-45 min session involving 5 different tasks designed to train executive functions and attention, available at the Guttmann Neuropersonaltrainer platform (computerized cognitive training tool certified by the Spanish Agency for Medicines and Health Products as a Class I Health Product). The difficulty level of all the tasks was automatically adjusted on a trial-by-trial basis for both Active and Active Control conditions.<br>Device: transcranial Direct-Current Stimulation (tDCS)<br>* tDCS: 4 consecutive days, 20 min session, delivered through multichannel tDCS (Starstim, Neuroelectrics), with an excitatory target over the r-dlPFC, and an inhibitory target on the contralateral lobe (l-dlPFC). The positioning of the multichannel tCS (electrode location and currents) was solved using the Stimweaver (Ruffini 2013). The resulting tCS montage employed 8 gelled Ag/AgCl electrodes of π cm2 size (Pistim, Neuroelectrics) placed at AF3(-1093uA), AF4 (1178uA), F3 (-1161uA), F4 (1104uA), F7 (-414uA), F8 (530uA), FC5 (1189uA), FC6 (-1332uA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in food intake | Changes in food consumption (medium kcal intake ) from baseline to the end of the treatment measured by 4-day food registers during the week before starting the treatment and during the 4 days of treatment. The dietary records were checked by a nutritionist and analyzed through the software PCN Pro 1.0. | 4 consecutive days during the week before starting the treatment; 4 consecutive days during the week of treatment; | 
| Stability of changes in food intake | Changes in food consumption (medium kcal intake ) from baseline to the follow-up assessment measured by 4-day food registers during the week before starting the treatment and the week after finishing the treatment. The dietary records were checked by a nutritionist and analyzed through the software PCN Pro 1.0. | 4 consecutive days during the week before starting the treatment and 4 consecutive days during the week after finishing the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in electroencephalogram (EEG) power and coherence | EEG was recorded before and after tCS/sham using a Starstim device (Neuroelectrics), same electrode positions as for the stimulation with a sampling frequency of 500 S/s . Electrode impedance: below 10kΩ; electrical reference placed at the right earlobe. EEG data was analyzed offline by means of customized Matlab code (MathWorks Inc. Natick, MA, USA). Data was split into 1s non-overlapping epochs (epochs with amplitudes >50 μV were rejected). EEG-metrics extracted: EEG-power and coherence. To compute EEG power, the power spectral density (PSD) was estimated for each epoch. Band Power was computed for the bands θ=[4,8 Hz], α=[8,13 Hz] β=[13,25 Hz], γ=[30, 45 Hz] and broadband=[4-45Hz] by integrating the PSD within the band frequency limits. Functional connectivity was estimated by means of coherence by the Welch method averaged over all electrodes. Frontal asymmetry (FA) computed as follows: log(avg(AF4 F4 F8 FC6))-log(avg(AF3 F3 F7 FC5); FA<0 reflects dominance of left-hemisphere | Every training session (4 consecutive days), 3 minutes before starting the training session and 3 minutes after finishing the training. | 
| Change in Body Mass Index (BMI) | Change in BMI. BMI calculation: body weight divided by the square of the body height (expressed in units of kg/m2). Weight and height measures were taken by a nurse. | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) | 
| Change in endocannabinoids (and related compounds) plasmatic concentrations. | Change in endocannabinoids and related compounds (acylglycerols and fatty acid N-acylethanolamides) as measured in plasmatic concentrations and quantified by LC/MS-MS by a previously validated method (Pastor et al. 2014). | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) | 
| Change in hormonal measurements : Leptin and adiponectin plasmatic/serum concentrations | Measurement of change in hormones regulating the appetite and energic homeostasis of secretion in fatty tissues. | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) | 
| Change in neuropsychological test: Intra-extra dimension (IED-CANTAB Cambridge Cognition) | Executive functions: flexibility | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) | 
| Change in neuropsychological test: Stroop Colours and Words test (SCWT, Golden C.J., 1978; Stroop, 1935) | Executive functions: inhibition | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) | 
| Change in neuropsychological test: Iowa Gambling Task (IGT, Bechara et al., 1994, 2002) | Executive functions: decision-making, risky behaviour. | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) | 
| Change in neuropsychological test: Spatial Span (SSP; CANTAB Cambridge Cognition) | Executive functions: working memory | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) | 
| Change in neuropsychological test: Stockings of Cambridge (SOC; CANTAB Cambridge Cognition) | Executive functions: planning | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) | 
| Change in neuropsychological test: Conners Continuous Performance Test (CPT, Conners & MHS Staff, 2000) | Executive functions: Attention | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) | 
| Change in neuropsychological test: Simple Reaction Time (SRT; CANTAB Cambridge Cognition) | Executive functions: Attention | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) | 
| Change in neuropsychological test:Symbol digit modalities test (SDMT; Smith A. 1982). | Executive functions: Attention and Processing speed | One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment) |