## Protocol Section
### Identification Module
**NCT ID:** NCT03943979

**Brief Title:** Pilot Study of an Intervention Involving Cognitive Training and tDCS in Morbidly Obese Subjects

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

#### Organization Study ID Info
**ID:** IMIMFTLC/EC-TDCS OM
#### Organization
**Class:** OTHER
**Full Name:** Parc de Salut Mar
### Status Module
#### Completion Date
**Date:** 2017-06-01

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2019-05-09

**Type:** ACTUAL

**Last Update Submit Date:** 2019-05-08

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2017-05-26

**Type:** ACTUAL

#### Start Date
**Date:** 2016-02-25

**Type:** ACTUAL

**Status Verified Date:** 2019-05

#### Study First Post Date
**Date:** 2019-05-09
**Type:** ACTUAL
**Study First Submit Date:** 2018-06-14
**Study First Submit QC Date:** 2019-05-08
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Neuroelectrics Corporation

#### Lead Sponsor

**Class:** OTHER

**Name:** Parc de Salut Mar

#### Responsible Party

**Investigator Affiliation:** Parc de Salut Mar

**Investigator Full Name:** Albert Goday Arno

**Investigator Title:** Medical doctor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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:** 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.

### Conditions Module

**Conditions:**

- Obesity, Morbid

- Obesity (BMI > 35) and Diabetes Mellitus

- Obesity (BMI > 35) and High Blood Pressure

- Obesity (BMI > 35) and Dyslipemia

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention 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 Info

**Masking:** QUADRUPLE

**Masking Description:** The difference between the two groups is the tDCS therapy. To mask this difference, the duration time of the session will be the same under both conditions but a standard Sham tDCS protocol will be used for the Active Control group. That is, a 3-sec ramp-up and ramp-down current stimulation, so the subject perceives the current just like the real tDCS, but it is not strong nor durable enough to have any effect on the neuronal activity.

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 18

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** This group will receive CT and sham tDCS each day, for four days.

**Intervention Names:**

- Other: Cognitive Training

**Label:** Active Control group

**Type:** SHAM_COMPARATOR

#### Arm Group 2

**Description:** This group will receive both CT and tDCS, each day, for four days.

**Intervention Names:**

- Other: Cognitive Training

- Device: transcranial Direct-Current Stimulation (tDCS)

**Label:** Active group

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Active Control group

- Active group

**Description:** 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.

**Name:** Cognitive Training

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- Active group

**Description:** 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).

**Name:** transcranial Direct-Current Stimulation (tDCS)

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** Change in food intake

**Time Frame:** 4 consecutive days during the week before starting the treatment; 4 consecutive days during the week of treatment;

**Description:** 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.

**Measure:** Stability of changes in food intake

**Time Frame:** 4 consecutive days during the week before starting the treatment and 4 consecutive days during the week after finishing the treatment

#### Secondary Outcomes

**Description:** 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

**Measure:** Change in electroencephalogram (EEG) power and coherence

**Time Frame:** Every training session (4 consecutive days), 3 minutes before starting the training session and 3 minutes after finishing the training.

**Description:** 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.

**Measure:** Change in Body Mass Index (BMI)

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

**Description:** 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).

**Measure:** Change in endocannabinoids (and related compounds) plasmatic concentrations.

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

**Description:** Measurement of change in hormones regulating the appetite and energic homeostasis of secretion in fatty tissues.

**Measure:** Change in hormonal measurements : Leptin and adiponectin plasmatic/serum concentrations

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

**Description:** Executive functions: flexibility

**Measure:** Change in neuropsychological test: Intra-extra dimension (IED-CANTAB Cambridge Cognition)

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

**Description:** Executive functions: inhibition

**Measure:** Change in neuropsychological test: Stroop Colours and Words test (SCWT, Golden C.J., 1978; Stroop, 1935)

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

**Description:** Executive functions: decision-making, risky behaviour.

**Measure:** Change in neuropsychological test: Iowa Gambling Task (IGT, Bechara et al., 1994, 2002)

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

**Description:** Executive functions: working memory

**Measure:** Change in neuropsychological test: Spatial Span (SSP; CANTAB Cambridge Cognition)

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

**Description:** Executive functions: planning

**Measure:** Change in neuropsychological test: Stockings of Cambridge (SOC; CANTAB Cambridge Cognition)

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

**Description:** Executive functions: Attention

**Measure:** Change in neuropsychological test: Conners Continuous Performance Test (CPT, Conners & MHS Staff, 2000)

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

**Description:** Executive functions: Attention

**Measure:** Change in neuropsychological test: Simple Reaction Time (SRT; CANTAB Cambridge Cognition)

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

**Description:** Executive functions: Attention and Processing speed

**Measure:** Change in neuropsychological test:Symbol digit modalities test (SDMT; Smith A. 1982).

**Time Frame:** One day during the week before starting the training (pre-treatment) and the 1 day after finishing the treatment (post-treatment)

### Eligibility Module

**Eligibility Criteria:** 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.

**Healthy Volunteers:** True

**Maximum Age:** 60 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Alonso-Alonso M. Translating tDCS into the field of obesity: mechanism-driven approaches. Front Hum Neurosci. 2013 Aug 27;7:512. doi: 10.3389/fnhum.2013.00512. eCollection 2013.

**PMID:** 23986687

**Citation:** Barr MS, Fitzgerald PB, Farzan F, George TP, Daskalakis ZJ. Transcranial magnetic stimulation to understand the pathophysiology and treatment of substance use disorders. Curr Drug Abuse Rev. 2008 Nov;1(3):328-39. doi: 10.2174/1874473710801030328.

**PMID:** 19630729

**Citation:** Boivin JR, Piscopo DM, Wilbrecht L. Brief cognitive training interventions in young adulthood promote long-term resilience to drug-seeking behavior. Neuropharmacology. 2015 Oct;97:404-13. doi: 10.1016/j.neuropharm.2015.05.036. Epub 2015 Jun 9.

**PMID:** 26066577

**Citation:** Conti CL, Moscon JA, Fregni F, Nitsche MA, Nakamura-Palacios EM. Cognitive related electrophysiological changes induced by non-invasive cortical electrical stimulation in crack-cocaine addiction. Int J Neuropsychopharmacol. 2014 Sep;17(9):1465-75. doi: 10.1017/S1461145714000522. Epub 2014 Apr 28.

**PMID:** 24776374

**Citation:** Corbett A, Owen A, Hampshire A, Grahn J, Stenton R, Dajani S, Burns A, Howard R, Williams N, Williams G, Ballard C. The Effect of an Online Cognitive Training Package in Healthy Older Adults: An Online Randomized Controlled Trial. J Am Med Dir Assoc. 2015 Nov 1;16(11):990-7. doi: 10.1016/j.jamda.2015.06.014.

**PMID:** 26543007

**Citation:** Ditye T, Jacobson L, Walsh V, Lavidor M. Modulating behavioral inhibition by tDCS combined with cognitive training. Exp Brain Res. 2012 Jun;219(3):363-8. doi: 10.1007/s00221-012-3098-4. Epub 2012 Apr 25.

**PMID:** 22532165

**Citation:** Gluck ME, Alonso-Alonso M, Piaggi P, Weise CM, Jumpertz-von Schwartzenberg R, Reinhardt M, Wassermann EM, Venti CA, Votruba SB, Krakoff J. Neuromodulation targeted to the prefrontal cortex induces changes in energy intake and weight loss in obesity. Obesity (Silver Spring). 2015 Nov;23(11):2149-56. doi: 10.1002/oby.21313.

**PMID:** 26530931

**Citation:** Goldman RL, Borckardt JJ, Frohman HA, O'Neil PM, Madan A, Campbell LK, Budak A, George MS. Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving. Appetite. 2011 Jun;56(3):741-6. doi: 10.1016/j.appet.2011.02.013. Epub 2011 Feb 23.

**PMID:** 21352881

**Citation:** Grall-Bronnec M, Sauvaget A. The use of repetitive transcranial magnetic stimulation for modulating craving and addictive behaviours: a critical literature review of efficacy, technical and methodological considerations. Neurosci Biobehav Rev. 2014 Nov;47:592-613. doi: 10.1016/j.neubiorev.2014.10.013.

**PMID:** 25454360

**Citation:** Jauch-Chara K, Kistenmacher A, Herzog N, Schwarz M, Schweiger U, Oltmanns KM. Repetitive electric brain stimulation reduces food intake in humans. Am J Clin Nutr. 2014 Oct;100(4):1003-9. doi: 10.3945/ajcn.113.075481. Epub 2014 Aug 6.

**PMID:** 25099550

**Citation:** Juarascio AS, Manasse SM, Espel HM, Kerrigan SG, Forman EM. Could training executive function improve treatment outcomes for eating disorders? Appetite. 2015 Jul;90:187-93. doi: 10.1016/j.appet.2015.03.013. Epub 2015 Mar 14.

**PMID:** 25777264

**Citation:** Sauvaget A, Trojak B, Bulteau S, Jimenez-Murcia S, Fernandez-Aranda F, Wolz I, Menchon JM, Achab S, Vanelle JM, Grall-Bronnec M. Transcranial direct current stimulation (tDCS) in behavioral and food addiction: a systematic review of efficacy, technical, and methodological issues. Front Neurosci. 2015 Oct 9;9:349. doi: 10.3389/fnins.2015.00349. eCollection 2015.

**PMID:** 26500478

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000050177

- Term: Overweight

- ID: D000044343

- Term: Overnutrition

- ID: D000009748

- Term: Nutrition Disorders

- ID: D000001835

- Term: Body Weight

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: LOW

- As Found: Unknown

- ID: M10024

- Name: Hypertension

- Relevance: HIGH

- As Found: High Blood Pressure

- ID: M12701

- Name: Obesity

- Relevance: HIGH

- As Found: Obesity

- ID: M12702

- Name: Obesity, Morbid

- Relevance: HIGH

- As Found: Obesity, Morbid

- ID: M26186

- Name: Overweight

- Relevance: LOW

- As Found: Unknown

- ID: M25307

- Name: Overnutrition

- Relevance: LOW

- As Found: Unknown

- ID: M12684

- Name: Nutrition Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5114

- Name: Body Weight

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006973

- Term: Hypertension

- ID: D000009765

- Term: Obesity

- ID: D000009767

- Term: Obesity, Morbid

### Misc Info Module

- Version Holder: 2024-05-24
