The Effects of Repetitive Transcranial Magnetic Stimulation in Obese People With BED

Study Overview
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Brief Summary
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The presence of binge eating (BE) is a core feature of bulimic syndromes. Binge eating disorder (BED) is a new category in DSM-5 highly associated with higher body mass index (BMI). The neural mechanisms that underlie BE are of great interest in order to improve treatment interventions. Brain mechanisms underlying drug and food craving are suggested to be similar. These mechanisms demonstrated hyperactivity in the orbitofrontal and anterior cingulate cortex and lack of regulatory influence from lateral prefrontal circuits. Several novel studies began to assess the potential benefits of brain stimulation in reducing craving and associated addictive behaviors with promising results. Previous findings testing a one-off session of repetitive transcranial magnetic stimulation (rTMS) in healthy women identified as strong cravers and individuals with bulimia nervosa or bulimic-type eating disorders reported reduction of food craving and BE, providing evidence to support a broader and deeper investigation of the benefits associated with rTMS. Importantly, the use of brain imaging studies contributes to the understanding of psychiatric disorders and underlying mechanisms being target by the rTMS intervention. Objectives: The primary aim is to investigate the effects of rTMS over BE frequency. Secondary aims include the evaluation of the effects of rTMS on food craving, body weight, brain activity, cognition, general psychopathology, hormonal regulation and neurobiological markers. Methods: Sixty obese females with BED will be randomized to receive 20 sessions of rTMS (n=30) or placebo (n=30) scattered 3 days/week. Expected Results: Primarily it is expected that rTMS intervention will decrease BE frequency. Consequently, body weight will be reduced. It is also expected that food craving be decreased, cognitive performance be enhanced, and neurobiological markers be improved.

Detailed Description
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The primary aim is to investigate the effects of rTMS over BE frequency. Secondary aims include the evaluation of the effects of rTMS on food craving, body weight, brain activity, cognition, general psychopathology, hormonal regulation and neurobiological markers. Methods: Sixty obese females with BED will be randomized to receive 20 sessions of rTMS (n=30) or placebo (n=30) scattered 3 days/week. Expected Results: Primarily it is expected that rTMS intervention will decrease BE frequency. Consequently, body weight will be reduced. It is also expected that food craving be decreased, cognitive performance be enhanced, and neurobiological markers be improved.

Official Title
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The Effects of Repetitive Transcranial Magnetic Stimulation in Obese Females With Binge Eating Disorder: a Protocol for a Double-blinded, Randomized, Sham-controlled Trial.

Conditions
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Binge Eating, Obesity

Intervention / Treatment
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* Device: TMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 55 years old Right handed Females BED diagnosis (EDE 16.0 - BED module) according to the DSM-5 criteria BMI ≥ 35kg/m2 and body weight ≤ 150kg Ability to write, read, and understand all elements of the study Safety laboratory blood work (fasting glucose, fasting glucose/insulin ratio, CBC, and TSH) within normal range Informed consent signed. Exclusion Criteria: Past history of head or eye injury or epilepsy Body metallic implants, pacemaker, claustrophobia and any other contraindication to fMRI or rTMS; Current use of psychotropic drugs (except for antidepressants on a stable dose for at least one month) Current use of any anti-obesity drug (three months washout period for any other medication) Pregnancy or breastfeeding Diabetes Mellitus diagnosis Major psychiatric disorder requiring immediate treatment Substance dependence (SCID-I/P module for substance abuse and/or dependence applied for those who disclose substance use at checklist, following the DSM-5 criteria) Individuals currently receiving any psychological therapy for their eating disorder Cushing's and Turner's syndrome.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

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: Repetitive transcranial magnetic stimulation applied to people with binge eating disorder (real x sham stimulation) only (not for control groups without binge eating disorder)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BED randomized to rTMS<br>30 obese individuals currently diagnosed with BED and meeting criteria for the study will be randomized to active rTMS treatment. Intervention: Neurosoft device targeting the left DLPFC (neuro-navigational method). Proposed schedule of treatment: 20 sessions of neuronavigated rTMS, one session per day, 3 days/week over approximately 7 weeks. Focal rTMS will be performed using a Neurosoft device and a 'figure of eight' coil. Brainscience Neuronavigation will be used to guide the placement of the coil to the target PFC region using a template MRI for all participants. The coil will be placed at a 45° angle to the mid-sagittal line to induce a posterior to anterior current in the underlying neural tissue. For the real treatment condition, stimulation will target the left DLPFC at 110% of the resting motor threshold. Each session of 10 Hz stimulation will apply 1000 pulses to the left hemisphere, with a duty cycle of 5s on and 55s off, for a total stimulation time of 20 min. | Device: TMS<br>* Transcranial Magnetic Stimulation has developed into a powerful tool that utilizes magnetic fluxes to non-invasively stimulate the human cortex. The technique involves placement of a small coil over the scalp; passing a rapidly alternating current through the coil wire, which produces a magnetic field that passes unimpeded through the scalp and bone, resulting in electrical stimulation of the cortex.<br>* Other names: rTMS;|
| Sham Comparator: Sham BED TMS<br>30 obese individuals currently diagnosed with BED will be randomized to receive sham TMS treatment. Blinded to participants and study staff, except to the doctor applying the TMS treatment. Intervention: Neurosoft device targeting the left DLPFC (neuro-navigational method). Proposed schedule of treatment: 20 sessions of neuronavigated rTMS, one session per day, 3 days/week over approximately 7 weeks. Focal rTMS will be performed using a Neurosoft device and a 'figure of eight' coil. Brainscience Neuronavigation will be used to guide the placement of the coil to the target PFC region using a template MRI for all participants. The coil will be placed at a 45° angle to the mid-sagittal line to induce a posterior to anterior current in the underlying neural tissue. Sham treatment condition, will follow the same protocol however no real TMS will be delivered. | Device: TMS<br>* Transcranial Magnetic Stimulation has developed into a powerful tool that utilizes magnetic fluxes to non-invasively stimulate the human cortex. The technique involves placement of a small coil over the scalp; passing a rapidly alternating current through the coil wire, which produces a magnetic field that passes unimpeded through the scalp and bone, resulting in electrical stimulation of the cortex.<br>* Other names: rTMS;|
| No Intervention: Control (obese non BED)<br>15 controls, obese but without a current or past diagnosis of BED will complete the baseline measurements only. | |
| No Intervention: Controls (normal weight)<br>15 controls, normal weight and without a current or past diagnosis of BED will complete baseline measures only. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the number of binge eating episodes and craving. | Weekly binge eating episodes frequency will be assessed by the medical doctor. The primary outcomes of this study are: (1) the change in the number of BE episodes before and after study treatment (number of BE episodes at baseline subtracted from the number of BE episodes at the end of treatment), as measured by participants recording of binge episodes in the food diary during the previous 15 days to the baseline visit (first rTMS session,T.3) to the end of treatment visit (T.23); (2) the change in urge to eat (craving) as measured in a 10 cm VAS (from T3 to T22). | Average of 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of food craving questionnaires (state and trait) scores | Food craving questionnaires scores will be analyzes at baseline and at the end of the treatment (approximately 2 months). Final scores for each of the participants will be subtracted from the baseline scores. | Average of 2 months (baseline and end of treatment) | 
| Change in Body Weight | Reduction of baseline body weight (kg) at the end of the treatment (average of 2 months). The final weight will be subtracted from the baseline weight for each of the patients. | Average of 2 months | 
| Binge eating episodes maintenance | Weekly binge eating episodes frequency will be recorded by participants. Participants will asked to record date, time and description of binge eating episodes. The total number of episodes and frequency distribution for each of the groups will be analyzed. | 8 weeks follow up (after end of treatment) | 
| Change of visual analogue scale scores | visual analogue scale scores will be analyzes at baseline and at the end of the treatment (approximately 2 months). Final scores for each of the participants will be subtracted from the baseline scores. | Average of 2 months (baseline and end of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Binge Eating, Obesity, TMS, Neuroimage, Neuromodulation, Biomarkers, Eating Disorders, Cognition, Endocrine, Hormones, BDNF, Inflammatory biomarkers