Clinical trial NCT02953353: Noninvasive Neuromodulation of the Prefrontal Cortex in Subjects With Obesity
Official title: Noninvasive Neuromodulation of the Prefrontal Cortex in Subjects With Obesity: a Proof-of-concept Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: Obesity
Feeding behavior
Transcranial direct current stimulation
Weight loss
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
name: Beth Israel Deaconess Medical Center
name: USDA Human Nutrition Research Center on Aging
First posted: 2016-11-02
Enrollment: 38
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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:

1. 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.
2. 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.
3. 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.
4. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Body weight
timeFrame: 6 months
Secondary outcomes:
measure: Appetite visual analogue scale
timeFrame: 6 months
measure: Eating behavior questionnaire
timeFrame: 6 months
measure: Cognitive performance in a food modified working memory test
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Human Nutrition Research Center on Aging, Tufts University
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center, Harvard Medical School
state: Massachusetts
city: Ribeirão Preto
country: Brazil
facility: Clinical Hospital of Ribeirão Preto
state: São Paulo
Study officials:
affiliation: University of Sao Paulo
name: Vivian MM Suen, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Human Nutrition Research Center on Aging, Tufts University
name: Sai K Das, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School
name: Miguel Alonso-Alonso, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Truong DQ, Magerowski G, Pascual-Leone A, Alonso-Alonso M, Bikson M. Finite Element study of skin and fat delineation in an obese subject for transcranial Direct Current Stimulation. Annu Int Conf IEEE Eng Med Biol Soc. 2012;2012:6587-90. doi: 10.1109/EMBC.2012.6347504.
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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.
citation: Val-Laillet D, Aarts E, Weber B, Ferrari M, Quaresima V, Stoeckel LE, Alonso-Alonso M, Audette M, Malbert CH, Stice E. Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity. Neuroimage Clin. 2015 Mar 24;8:1-31. doi: 10.1016/j.nicl.2015.03.016. eCollection 2015.