Deep Transcranial Magnetic Stimulation (TMS) With Paired Associative Stimulation (PAS) for the Treatment of Food Addiction in Obesity

Study Overview
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Brief Summary
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The neurobiological underpinnings of obesity point to brain asymmetry in cortical and deeper brain regions. Furthermore, chemical, structural and functional imbalance in cortical and sub-cortical brain regions alters reward processing, attentional control and self-regulation in food-addicted obese individuals. In this study the investigators use TMS with a special multichannel H-coil developed by their lab to safely stimulate cortical and deeper brain regions in obese humans. The investigators aim to produce interhemispheric neuroplasticity (INP) using a paired associative stimulation (PAS) protocol over the DLPFC, to restore neurobiological functioning, alleviate food addiction symptoms, and promote weight loss.

Official Title
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Comparison of Two Deep TMS Protocols With Paired Associative Stimulation (PAS) for the Treatment of Food Addiction in Severe Obesity

Conditions
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Obesity

Intervention / Treatment
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* Device: A multi-channel deep TMS device with an H-coil (Brainsway Ltd)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 30 ≤ BMI ≥ 40. Having had at least one prior conventional weight loss attempt, but no current weight loss attempts or over the last 3 months. Having satisfied a safety screening questionnaire for TMS (Keel, 2001) Omnivorous Have not had experience with TMS of any kind Exclusion Criteria: The participant experiences tremor in any limb. The participant experiences seizures. The participant has a history of epilepsy or seizure (EXCEPT those therapeutically induced by ECT), or a history of such in first degree relatives. The participant is at increased risk for seizures for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or a history of significant head trauma with loss of consciousness for > 5 minutes. The participant has a history of head injury. The participant suffers from an unstable physical disease, such as high blood pressure (>150 mmHg systolic / diastolic > 110 mmHg) or acute, unstable cardiac disease The participant is at a high risk for severe violence or suicidal tendencies, assessed during the screening interview (see appendix 4). The participant has metallic particles in the eye, implanted cardiac pacemaker or any intracardiac lines, implanted neuro-stimulators, intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or implanted medical pumps. The participant is having, or has had, any metal in the head (outside the mouth). The participant suffers from a significant neurological disorder or insult including, but not limited to: Any condition likely to be associated with increased intracranial pressure Space occupying brain lesion History of cerebrovascular accident Transient ischemic attack within the last two years Cerebral aneurysm Dementia Parkinson's disease Huntington's chorea Multiple sclerosis The participant has any cognitive or functional disability, according to criteria specified in the DSM-V, such as active psychiatric disorder according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-V; Axis I and Axis II) diagnosed within the last year. The participant has started or changed a psychotropic prescription within the last three months. The participant has current alcohol or other substance abuse or dependence, or has had one over the last 12 months prior to recruitment. The participant can't reliably communicate with the investigator, or is unlikely to cope with the requirements of the experiment. The participant is having a known or suspected pregnancy or lactation. The participant is a sexually-active woman of childbearing age, who does not use a medically accepted form of contraception. The motor threshold can't be found or quantified. The PI decides that the participant should be withdrawn from the study for the safety and welfare of the participant. For example, the participant experiences adverse event which is contraindicated with the continuation in the study. A history of intolerance to a TMS treatment. The participant asks for withdrawal

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 70 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A PAS protocol, right-to-left, via deep TMS<br>Via a multi-channel deep TMS device with an H-coil (Brainsway Ltd), a PAS protocol, starting with the right DLPFC | Device: A multi-channel deep TMS device with an H-coil (Brainsway Ltd)<br>* A 3-week long treatment (15 days). Treatment session consist of 300 rapidly occurring pairs of pulses over the dorsolateral prefrontal cortex (at a frequency of 10 Hz and intensity of 110% of individual's motor threshold), with a 5-seconds interval, for a duration of 1800 seconds in total.<br>|
| Experimental: A PAS protocol, left-to-right, via deep TMS<br>Via a multi-channel deep TMS device with an H-coil (Brainsway Ltd), a PAS protocol, starting with the left DLPFC | Device: A multi-channel deep TMS device with an H-coil (Brainsway Ltd)<br>* A 3-week long treatment (15 days). Treatment session consist of 300 rapidly occurring pairs of pulses over the dorsolateral prefrontal cortex (at a frequency of 10 Hz and intensity of 110% of individual's motor threshold), with a 5-seconds interval, for a duration of 1800 seconds in total.<br>|
| Sham Comparator: A sham PAS protocol, via deep TMS<br>Via a multi-channel deep TMS device with an H-coil (Brainsway Ltd), a sham PAS protocol, starting with the right DLPFC (@ 40% of individual MT) | Device: A multi-channel deep TMS device with an H-coil (Brainsway Ltd)<br>* A 3-week long treatment (15 days). Treatment session consist of 300 rapidly occurring pairs of pulses over the dorsolateral prefrontal cortex (at a frequency of 10 Hz and intensity of 110% of individual's motor threshold), with a 5-seconds interval, for a duration of 1800 seconds in total.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight | Unit of measure: BMI in kg/m^2 (weight in kilograms, height in meters) | Change in weight between baseline versus the end of the treatment (day 15) and follow-up (a month after day 15) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance on a food Stroop test | Unit of measure: reaction time (in milliseconds) | Change in performance between baseline versus the end of the treatment (day 15) and follow-up (a month after day 15) | 
| Food addiction symptoms | Yale Food Addiction Scale (YFAS) | Change between baseline versus the end of the treatment (day 15) and follow-up (a month after day 15) | 
| Safety and tolerability of a PAS protocol using the multi-channel deep TMS system, measured via the number of adverse events (AE) | Measured via the number of adverse events | Throughout the study period, estimated as 2 years | 
| Eating behavior (cognitive restraint, disinhibition, and hunger) | Three Factor Eating Questionnaire (TFEQ) | Change between baseline versus the end of the treatment (day 15) and follow-up (a month after day 15) | 
| Quality of life | Health Status Scale Short-form 36 (SF-36) | Change between baseline and the end of the treatment (day 15) and follow-up (a month after day 15) | 
| Implementation of INP | 1. Acute change in INP, assessed via changes in cortical excitability (measured via EEG and TCI) between pre- and post PAS administration. 2. Chronic change in INP assessed as change in cortical excitability between baseline versus the end of the treatment (day 15) and follow up (measured via EEG and TCI) | Changes in cortical excitability between baseline versus following 15 days of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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food addiction, obesity, deep TMS, PAS, Food Stroop, brain laterality, EEG, INP