<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03009695</url>
  </required_header>
  <id_info>
    <org_study_id>SMT/obesi</org_study_id>
    <nct_id>NCT03009695</nct_id>
  </id_info>
  <brief_title>Transcranial Magnetic Stimulation (TMS) in Obesity</brief_title>
  <official_title>Impact of Deep Transcranial Magnetic Stimulation (dTMS) on Satiety and Weight Control</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ospedale San Donato</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ospedale San Donato</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Obesity is a metabolic disease that has reached epidemic proportions. Insofar no long-term&#xD;
      effective drug treatment was developed for obesity. Lyfe style modulation and bariatric&#xD;
      surgery are the only interventions with a limited rate of success. Obesity is due to several&#xD;
      factors, mainly linked to a neurophysiological mechanism of &quot;food addiction&quot;. The use of&#xD;
      repetitive deep Transcranial Magnetic Stimulation (dTMS) was proposed to reduce appetite and&#xD;
      food craving in obese subjects, leading eventually to a weight reduction. dTMS was already&#xD;
      tested successfully in other forms of addiction (smoking, alcohol, cocaine) and the&#xD;
      usefulness of dTMS in the treatment of food addiction, and therefore in obesity, was&#xD;
      hypothesized. End-points of this research will be: 1) effect on food craving; 2) acute and&#xD;
      chronic effects on blood level of hormones acting on the appetite regulation; 3) chronic&#xD;
      effects on body weight. The demonstration that a safe, non-invasive and repeatable&#xD;
      methodology can treat obesity reducing food craving and modulating appetite/satiety hormones&#xD;
      secretion will constitute a cornerstone in translational medicine of metabolic diseases.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>February 2015</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in food craving levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Food craving will be evaluated by the Food Cravings Questionnaire-Trait (FCQ-T), a self-report multidimensional questionnaire composed of 39 items aimed to investigate food addiction and eating disorders. Total FCQ-T score will be used as a general measure of trait craving; individual FCQ-T scores related to the 9 measured craving dimensions could be useful in identifying and differentiating craving profiles between specific populations. Food craving will be also evaluated at follow-up visit 1 (1 month after the end of treatment), follow-up visit 2 (6 months after the end of treatment), and follow-up visit 3 (1 year after the end of treatment).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in body weight induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To evaluate the effectiveness of repetitive dTMS on body weight, the variation rate in kilograms of body weight between baseline and after 5 weeks will be considered. Body weight will be also evaluated at the 3 follow-up visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Fat Mass (FM) rate induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Changes in body composition, specifically in FM percentage (%), will be evaluated by body densitometry at the end of treatment compared to baseline. FM rate will be also evaluated at the follow-up visit 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute and chronic changes in insulin levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: insulin (microU/mL). Insulin will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute and chronic changes in glucagon levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: glucagon (pg/mL). Glucagon will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute and chronic changes in ghrelin levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: ghrelin (pg/mL). Ghrelin will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute and chronic changes in leptin levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: leptin (ng/mL). Leptin will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute and chronic changes in Growth Hormone (GH) levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: GH (ng/mL). GH will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute and chronic changes in Adreno-Cortico-Tropic Hormone (ACTH) levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: ACTH (pg/mL). ACTH will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute and chronic changes in Thyroid-Stimulating Hormone (TSH) levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: TSH (microUI/mL). TSH will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute and chronic changes in Prolactin levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: Prolactin (ng/mL). Prolactin will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute and chronic changes in Cortisol levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: Cortisol (microg/dL). Cortisol will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute and chronic changes in Neuropeptide Y levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: Neuropeptide Y (pg/mL). Neuropeptide Y will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Beta-endorphin levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Changes in neurophysiological mechanisms involved in satiety will be evaluated by dosing the main neurotransmitters involved in the reward system, like Beta-endorphins (ng/mL). Beta-endorphins will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Epinephrine levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Changes in neurophysiological mechanisms involved in satiety will be evaluated by dosing the main neurotransmitters involved in the reward system, like Epinephrine (pg/mL). Epinephrine will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Norepinephrine levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Changes in neurophysiological mechanisms involved in satiety will be evaluated by dosing the main neurotransmitters involved in the reward system, like Norepinephrine (pg/mL). Norepinephrine will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Glucose levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Changes in glucose metabolism will be evaluated by glucose (mg/dL). Glucose will be measured acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Glycated Hemoglobin levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Changes in glucose metabolism will be evaluated by Glycated Hemoglobin (mmol/mol). Glycated Hemoglobin will be measured chronically (at baseline, end of treatment and follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Cholesterol levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Changes in lipid metabolism will be evaluated by Cholesterol (mg/dL). Cholesterol will be measured acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Triglyceride levels induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Changes in lipid metabolism will be evaluated by Triglycerides (mg/dL). Triglycerides will be measured acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in Resting Energy Expenditure (REE) induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Changes in REE (Kcal/day) will be evaluated by Indirect Calorimetry. Indirect Calorimetry will be performed at baseline, at the end of treatment and at the follow-up visit 2.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in Activity Energy Expenditure (AEE) induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>AEE (Kcal/die) will be evaluated by an accelerometer. Minutes of activity, number of steps, traveled kilometers measurements will be aggregated to define AEE</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in cutaneous temperature induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Abdomen and nail bed of both hands temperature (°C) will be detected by infrared thermography</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in food cue-induced activation of specific brain areas induced by repetitive dTMS and detected by Magnetic Resonance Imaging (fMRI) from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>Cue-induced activation of specific brain areas will be evaluated by functional Magnetic Resonance Imaging (fMRI)</description>
  </other_outcome>
  <other_outcome>
    <measure>Assessment of adverse events</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>During all the study duration, participants will be asked if they are experiencing any adverse event (AE), serious adverse events (SAE) and un-expected serious adverse event (UESAE). All adverse events will be recorded in clinical record. SAE and UESAE will be communicated to Ethical Committee and Oversight Authorities. Number of participants experiencing adverse events will be recorded.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in gut microbiota composition induced by repetitive dTMS from baseline at 5 weeks</measure>
    <time_frame>Baseline and end of treatment (5 weeks)</time_frame>
    <description>A fecal sample will be collected at baseline and at the end of treatment (5 weeks) and gut microbiota analysis will be performed.</description>
  </other_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Obesity</condition>
  <condition>Food Craving</condition>
  <condition>Appetite and General Nutritional Disorders</condition>
  <arm_group>
    <arm_group_label>High frequency repetitive dTMS + Cue</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 obese individuals fulfilling all inclusion/exclusion criteria for the study will be randomized to active high frequency repetitive dTMS treatment with cue.&#xD;
Stimulation will be performed 3 times per week, for 5 weeks (15 treatments).&#xD;
In this group, stimulation will be performed with the following features:&#xD;
Intensity of stimulation: 120% of the resting Motor Threshold (rMT), Frequency: 18 Hz, Duration of the train: 2 sec, Inter-train interval: 20 sec, Trains number: 80, Total pulses: 2880, Total treatment duration: 29.3 min, Cue (sight of food preferred by patient): present.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High frequency repetitive dTMS - No Cue</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 obese individuals fulfilling all inclusion/exclusion criteria for the study will be randomized to active high frequency repetitive dTMS treatment without cue.&#xD;
Stimulation will be performed 3 times per week, for 5 weeks (15 treatments).&#xD;
In this group, stimulation will be performed with the following features:&#xD;
Intensity of stimulation: 120% of the resting Motor Threshold (rMT), Frequency: 18 Hz, Duration of the train: 2 sec, Inter-train interval: 20 sec, Trains number: 80, Total pulses: 2880, Total treatment duration: 29.3 min, Cue (sight of food preferred by patient): absent.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low frequency repetitive dTMS+ Cue</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 obese individuals fulfilling all inclusion/exclusion criteria for the study will be randomized to active low frequency repetitive dTMS treatment with cue.&#xD;
Stimulation will be performed 3 times per week, for 5 weeks (15 treatments).&#xD;
In this group, stimulation will be performed with the following features:&#xD;
Intensity of stimulation: 120% of the resting Motor Threshold (rMT) Frequency: 1 Hz Duration of the train: 10 min Inter-train interval: 1 min Trains number: 4 Total pulses: 2400 Total treatment duration: 43 min Cue (sight of food preferred by patient): present</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low frequency repetitive dTMS - No Cue</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 obese individuals fulfilling all inclusion/exclusion criteria for the study will be randomized to active low frequency repetitive dTMS treatment without cue.&#xD;
Stimulation will be performed 3 times per week, for 5 weeks (15 treatments).&#xD;
In this group, stimulation will be performed with the following features:&#xD;
Intensity of stimulation: 120% of the resting Motor Threshold (rMT), Frequency: 1 Hz, Duration of the train: 10 min, Inter-train interval: 1 min, Trains number: 4, Total pulses: 2400, Total treatment duration: 43 min, Cue (sight of food preferred by patient): absent.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>10 obese individuals fulfilling all inclusion/exclusion criteria for the study will be randomized to sham stimulation.&#xD;
Stimulation will be performed 3 times per week, for 5 weeks (15 treatments).&#xD;
In this group, stimulation will be performed with the following features:&#xD;
Intensity of stimulation: 120% of the resting Motor Threshold (rMT), Frequency: 18 Hz (50% of patients) and 1 Hz (50% of patients), Duration of the train: 2 sec or 10 min, Inter-train interval: 20 sec or 1 min, Trains number: 80 or 4, Total pulses: 2880 or 2400, Total treatment duration: 29.3 or 43 min, Cue (sight of food preferred by patient): present.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>High frequency repetitive dTMS</intervention_name>
    <description>Focal rTMS will be performed using a Magstim Rapid2 magnetic stimulator (The Magstim Co. Ltd., U.K.) equipped with an H-shaped coil. The used H-coil version is the H-addiction specifically designed to stimulate the insula and the Pre-Frontal Cortex (PFC). This novel H-coil allows direct stimulation of deeper brain regions, like insula (3 cm vs 1.5 cm from the skull). Before each stimulation the resting Motor Threshold (rMT) should be determined. The rMT will be determined over the left primary motor cortex, afterwards the coil will be moved forward 6 cm anterior the motor spot and aligned symmetrically over the PFC and insula. Repetitive dTMS induces long-lasting changes in neural excitability and dopamine release, specifically high-frequency rTMS (18 Hz) enhances cortical excitability.</description>
    <arm_group_label>High frequency repetitive dTMS + Cue</arm_group_label>
    <arm_group_label>High frequency repetitive dTMS - No Cue</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Low frequency repetitive dTMS</intervention_name>
    <description>Focal rTMS will be performed using a Magstim Rapid2 magnetic stimulator (The Magstim Co. Ltd., U.K.) equipped with an H-shaped coil. The used H-coil version is the H-addiction specifically designed to stimulate the insula and the Pre-Frontal Cortex (PFC). This novel H-coil allows direct stimulation of deeper brain regions, like insula (3 cm vs 1.5 cm from the skull). Before each stimulation the resting Motor Threshold (rMT) should be determined. The rMT will be determined over the left primary motor cortex, afterwards the coil will be moved forward 6 cm anterior the motor spot and aligned symmetrically over the PFC and insula. Repetitive dTMS induces long-lasting changes in neural excitability and dopamine release, specifically low-frequency rTMS (1 Hz) inhibits cortical excitability.</description>
    <arm_group_label>Low frequency repetitive dTMS - No Cue</arm_group_label>
    <arm_group_label>Low frequency repetitive dTMS+ Cue</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham</intervention_name>
    <description>Sham stimulation will be performed by an H-sham-coil. The H-sham-coil is designed to mimic the auditory artifacts and the scalp sensation evoked by the real coil, without stimulating the brain itself. As in the other groups, in each patient the rMT will be determined before each repetitive dTMS session. The sham stimulation will be performed either at high frequency (50% of subjects) or at low-frequency (50% of subjects), according to the previously described methodologies. All obese people in this group will be submitted at the sight of food preferred (cue).</description>
    <arm_group_label>Sham</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age: 22-65 years&#xD;
&#xD;
          2. If the patient is taking medications, it must take on a stable dose for at least a&#xD;
             month&#xD;
&#xD;
          3. Obesity: ≤ 30 BMI ≤ 45&#xD;
&#xD;
          4. Ability to follow verbal or written instructions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Axis-I and II psychiatric disorders according to DSM criteria 5 (such as Major&#xD;
             Depression, Bipolar Disorder, or Attention Deficit Disorder)&#xD;
&#xD;
          2. IQ score &lt; 85&#xD;
&#xD;
          3. Organic brain disorders: history of stroke, brain major surgery or head trauma&#xD;
&#xD;
          4. Pregnancy or lactation, absence of medically approved contraceptive methods in females&#xD;
             of childbearing potential&#xD;
&#xD;
          5. Serious or poorly controlled diseases (hepatic, renal or hearth failure, atrial&#xD;
             fibrillation or other heart rhythm disorders)&#xD;
&#xD;
          6. H yperglycemia - Fasting glucose level &gt; 170 mg/dl&#xD;
&#xD;
          7. Urine drug screen positive for amphetamines, barbiturates, cannabinoids, cocaine&#xD;
             metabolites, opiates and phencyclidine&#xD;
&#xD;
          8. Positivity to blood alcohol test&#xD;
&#xD;
          9. Metal in any part of the head, except for dental fillings&#xD;
&#xD;
         10. Implanted infusion pumps&#xD;
&#xD;
         11. Intracardiac devices (pacemakers, heart valves ...)&#xD;
&#xD;
         12. History of diseases whose exacerbation could be fatal (e.g. cardiovascular disease,&#xD;
             increased intracranial pressure)&#xD;
&#xD;
         13. History of epilepsy or a family history of epilepsy among first-degree relatives&#xD;
&#xD;
         14. Medications associated with lowered seizure threshold (such as antidepressants,&#xD;
             anxiolytics…)&#xD;
&#xD;
         15. Treatment with anti-obesity medications or other medications influencing body weight&#xD;
             within 3 month prior to Screening Visit&#xD;
&#xD;
         16. Starting a weight loss plan at any time during data collection for the subject&#xD;
&#xD;
         17. Patients affected by galactosemia, priapism and terminal illness&#xD;
&#xD;
         18. Patients on fluid restriction for SIADH or other conditions&#xD;
&#xD;
         19. Contraindications to perform the Magnetic Resonance Imaging (MRI).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Anna Ferrulli, M.D., Ph. D.</last_name>
    <phone>+39 3332742606</phone>
    <email>anna.ferrulli@grupposandonato.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Livio Luzi, Professor</last_name>
    <phone>+39 02-52774635</phone>
    <email>livio.luzi@unimi.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>San Donato Hospital</name>
      <address>
        <city>San Donato Milanese</city>
        <state>MI</state>
        <zip>20097</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Ferrulli, MD</last_name>
      <email>anna.ferrulli@grupposandonato.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Strafella AP, Paus T, Barrett J, Dagher A. Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci. 2001 Aug 1;21(15):RC157. doi: 10.1523/JNEUROSCI.21-15-j0003.2001.</citation>
    <PMID>11459878</PMID>
  </reference>
  <reference>
    <citation>Pascual-Leone A, Houser CM, Reese K, Shotland LI, Grafman J, Sato S, Valls-Sole J, Brasil-Neto JP, Wassermann EM, Cohen LG, et al. Safety of rapid-rate transcranial magnetic stimulation in normal volunteers. Electroencephalogr Clin Neurophysiol. 1993 Apr;89(2):120-30. doi: 10.1016/0168-5597(93)90094-6.</citation>
    <PMID>7683602</PMID>
  </reference>
  <reference>
    <citation>Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol. 1998 Jan;108(1):1-16. doi: 10.1016/s0168-5597(97)00096-8.</citation>
    <PMID>9474057</PMID>
  </reference>
  <reference>
    <citation>Zangen A, Roth Y, Voller B, Hallett M. Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil. Clin Neurophysiol. 2005 Apr;116(4):775-9. doi: 10.1016/j.clinph.2004.11.008. Epub 2004 Dec 16.</citation>
    <PMID>15792886</PMID>
  </reference>
  <reference>
    <citation>Innamorati M, Imperatori C, Balsamo M, Tamburello S, Belvederi Murri M, Contardi A, Tamburello A, Fabbricatore M. Food Cravings Questionnaire-Trait (FCQ-T) discriminates between obese and overweight patients with and without binge eating tendencies: the Italian version of the FCQ-T. J Pers Assess. 2014;96(6):632-9. doi: 10.1080/00223891.2014.909449. Epub 2014 May 2.</citation>
    <PMID>24793741</PMID>
  </reference>
  <reference>
    <citation>Uher R, Yoganathan D, Mogg A, Eranti SV, Treasure J, Campbell IC, McLoughlin DM, Schmidt U. Effect of left prefrontal repetitive transcranial magnetic stimulation on food craving. Biol Psychiatry. 2005 Nov 15;58(10):840-2. doi: 10.1016/j.biopsych.2005.05.043. Epub 2005 Aug 8.</citation>
    <PMID>16084855</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>26110109</PMID>
  </reference>
  <reference>
    <citation>Dinur-Klein L, Dannon P, Hadar A, Rosenberg O, Roth Y, Kotler M, Zangen A. Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: a prospective, randomized controlled trial. Biol Psychiatry. 2014 Nov 1;76(9):742-9. doi: 10.1016/j.biopsych.2014.05.020. Epub 2014 Jun 5.</citation>
    <PMID>25038985</PMID>
  </reference>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>December 4, 2016</study_first_submitted>
  <study_first_submitted_qc>January 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 4, 2017</study_first_posted>
  <last_update_submitted>September 6, 2018</last_update_submitted>
  <last_update_submitted_qc>September 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ospedale San Donato</investigator_affiliation>
    <investigator_full_name>Anna Ferrulli</investigator_full_name>
    <investigator_title>M.D., Ph.D, Sub-Investigator</investigator_title>
  </responsible_party>
  <keyword>Transcranial Magnetic Stimulation</keyword>
  <keyword>Obesity</keyword>
  <keyword>Food Craving</keyword>
  <keyword>Appetite/Satiety Hormones</keyword>
  <keyword>fMRI</keyword>
  <keyword>Intestinal microbiota</keyword>
  <keyword>Physical activity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
    <mesh_term>Nutrition Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03009695
org study id: SMT/obesi
nct id: NCT03009695
lead sponsor: 
has dmc: Yes
Obesity is a metabolic disease that has reached epidemic proportions. Insofar no long-term
      effective drug treatment was developed for obesity. Lyfe style modulation and bariatric
      surgery are the only interventions with a limited rate of success. Obesity is due to several
      factors, mainly linked to a neurophysiological mechanism of "food addiction". The use of
      repetitive deep Transcranial Magnetic Stimulation (dTMS) was proposed to reduce appetite and
      food craving in obese subjects, leading eventually to a weight reduction. dTMS was already
      tested successfully in other forms of addiction (smoking, alcohol, cocaine) and the
      usefulness of dTMS in the treatment of food addiction, and therefore in obesity, was
      hypothesized. End-points of this research will be: 1) effect on food craving; 2) acute and
      chronic effects on blood level of hormones acting on the appetite regulation; 3) chronic
      effects on body weight. The demonstration that a safe, non-invasive and repeatable
      methodology can treat obesity reducing food craving and modulating appetite/satiety hormones
      secretion will constitute a cornerstone in translational medicine of metabolic diseases.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Changes in food craving levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Food craving will be evaluated by the Food Cravings Questionnaire-Trait (FCQ-T), a self-report multidimensional questionnaire composed of 39 items aimed to investigate food addiction and eating disorders. Total FCQ-T score will be used as a general measure of trait craving; individual FCQ-T scores related to the 9 measured craving dimensions could be useful in identifying and differentiating craving profiles between specific populations. Food craving will be also evaluated at follow-up visit 1 (1 month after the end of treatment), follow-up visit 2 (6 months after the end of treatment), and follow-up visit 3 (1 year after the end of treatment).
measure: Changes in body weight induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To evaluate the effectiveness of repetitive dTMS on body weight, the variation rate in kilograms of body weight between baseline and after 5 weeks will be considered. Body weight will be also evaluated at the 3 follow-up visits.
measure: Changes in Fat Mass (FM) rate induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Changes in body composition, specifically in FM percentage (%), will be evaluated by body densitometry at the end of treatment compared to baseline. FM rate will be also evaluated at the follow-up visit 2
measure: Acute and chronic changes in insulin levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: insulin (microU/mL). Insulin will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).
measure: Acute and chronic changes in glucagon levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: glucagon (pg/mL). Glucagon will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).
measure: Acute and chronic changes in ghrelin levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: ghrelin (pg/mL). Ghrelin will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).
measure: Acute and chronic changes in leptin levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: leptin (ng/mL). Leptin will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).
measure: Acute and chronic changes in Growth Hormone (GH) levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: GH (ng/mL). GH will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).
measure: Acute and chronic changes in Adreno-Cortico-Tropic Hormone (ACTH) levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: ACTH (pg/mL). ACTH will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).
measure: Acute and chronic changes in Thyroid-Stimulating Hormone (TSH) levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: TSH (microUI/mL). TSH will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).
measure: Acute and chronic changes in Prolactin levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: Prolactin (ng/mL). Prolactin will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).
measure: Acute and chronic changes in Cortisol levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: Cortisol (microg/dL). Cortisol will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).
measure: Acute and chronic changes in Neuropeptide Y levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: To identify acute and chronic changes induced by repetitive dTMS on the neuro-endocrine pathway involved in the hunger/satiety balance, the following parameter will be considered: Neuropeptide Y (pg/mL). Neuropeptide Y will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, at end of treatment and at the 3 follow-up visits).
measure: Changes in Beta-endorphin levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Changes in neurophysiological mechanisms involved in satiety will be evaluated by dosing the main neurotransmitters involved in the reward system, like Beta-endorphins (ng/mL). Beta-endorphins will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).
measure: Changes in Epinephrine levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Changes in neurophysiological mechanisms involved in satiety will be evaluated by dosing the main neurotransmitters involved in the reward system, like Epinephrine (pg/mL). Epinephrine will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).
measure: Changes in Norepinephrine levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Changes in neurophysiological mechanisms involved in satiety will be evaluated by dosing the main neurotransmitters involved in the reward system, like Norepinephrine (pg/mL). Norepinephrine will be evaluated acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).
measure: Changes in Glucose levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Changes in glucose metabolism will be evaluated by glucose (mg/dL). Glucose will be measured acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).
measure: Changes in Glycated Hemoglobin levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Changes in glucose metabolism will be evaluated by Glycated Hemoglobin (mmol/mol). Glycated Hemoglobin will be measured chronically (at baseline, end of treatment and follow-up visits).
measure: Changes in Cholesterol levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Changes in lipid metabolism will be evaluated by Cholesterol (mg/dL). Cholesterol will be measured acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).
measure: Changes in Triglyceride levels induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Changes in lipid metabolism will be evaluated by Triglycerides (mg/dL). Triglycerides will be measured acutely (before and immediately after the first and the last rTMS sessions) and chronically (at baseline, end of treatment and follow-up visits).
measure: Changes in Resting Energy Expenditure (REE) induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Changes in REE (Kcal/day) will be evaluated by Indirect Calorimetry. Indirect Calorimetry will be performed at baseline, at the end of treatment and at the follow-up visit 2.
measure: Changes in Activity Energy Expenditure (AEE) induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: AEE (Kcal/die) will be evaluated by an accelerometer. Minutes of activity, number of steps, traveled kilometers measurements will be aggregated to define AEE
measure: Changes in cutaneous temperature induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Abdomen and nail bed of both hands temperature (°C) will be detected by infrared thermography
measure: Changes in food cue-induced activation of specific brain areas induced by repetitive dTMS and detected by Magnetic Resonance Imaging (fMRI) from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: Cue-induced activation of specific brain areas will be evaluated by functional Magnetic Resonance Imaging (fMRI)
measure: Assessment of adverse events
time frame: Through study completion, an average of 1 year
description: During all the study duration, participants will be asked if they are experiencing any adverse event (AE), serious adverse events (SAE) and un-expected serious adverse event (UESAE). All adverse events will be recorded in clinical record. SAE and UESAE will be communicated to Ethical Committee and Oversight Authorities. Number of participants experiencing adverse events will be recorded.
measure: Changes in gut microbiota composition induced by repetitive dTMS from baseline at 5 weeks
time frame: Baseline and end of treatment (5 weeks)
description: A fecal sample will be collected at baseline and at the end of treatment (5 weeks) and gut microbiota analysis will be performed.
arm group label: High frequency repetitive dTMS + Cue
arm group type: Experimental
description: 10 obese individuals fulfilling all inclusion/exclusion criteria for the study will be randomized to active high frequency repetitive dTMS treatment with cue.
Stimulation will be performed 3 times per week, for 5 weeks (15 treatments).
In this group, stimulation will be performed with the following features:
Intensity of stimulation: 120% of the resting Motor Threshold (rMT), Frequency: 18 Hz, Duration of the train: 2 sec, Inter-train interval: 20 sec, Trains number: 80, Total pulses: 2880, Total treatment duration: 29.3 min, Cue (sight of food preferred by patient): present.
arm group label: High frequency repetitive dTMS - No Cue
arm group type: Experimental
description: 10 obese individuals fulfilling all inclusion/exclusion criteria for the study will be randomized to active high frequency repetitive dTMS treatment without cue.
Stimulation will be performed 3 times per week, for 5 weeks (15 treatments).
In this group, stimulation will be performed with the following features:
Intensity of stimulation: 120% of the resting Motor Threshold (rMT), Frequency: 18 Hz, Duration of the train: 2 sec, Inter-train interval: 20 sec, Trains number: 80, Total pulses: 2880, Total treatment duration: 29.3 min, Cue (sight of food preferred by patient): absent.
arm group label: Low frequency repetitive dTMS+ Cue
arm group type: Experimental
description: 10 obese individuals fulfilling all inclusion/exclusion criteria for the study will be randomized to active low frequency repetitive dTMS treatment with cue.
Stimulation will be performed 3 times per week, for 5 weeks (15 treatments).
In this group, stimulation will be performed with the following features:
Intensity of stimulation: 120% of the resting Motor Threshold (rMT) Frequency: 1 Hz Duration of the train: 10 min Inter-train interval: 1 min Trains number: 4 Total pulses: 2400 Total treatment duration: 43 min Cue (sight of food preferred by patient): present
arm group label: Low frequency repetitive dTMS - No Cue
arm group type: Experimental
description: 10 obese individuals fulfilling all inclusion/exclusion criteria for the study will be randomized to active low frequency repetitive dTMS treatment without cue.
Stimulation will be performed 3 times per week, for 5 weeks (15 treatments).
In this group, stimulation will be performed with the following features:
Intensity of stimulation: 120% of the resting Motor Threshold (rMT), Frequency: 1 Hz, Duration of the train: 10 min, Inter-train interval: 1 min, Trains number: 4, Total pulses: 2400, Total treatment duration: 43 min, Cue (sight of food preferred by patient): absent.
arm group label: Sham
arm group type: Sham Comparator
description: 10 obese individuals fulfilling all inclusion/exclusion criteria for the study will be randomized to sham stimulation.
Stimulation will be performed 3 times per week, for 5 weeks (15 treatments).
In this group, stimulation will be performed with the following features:
Intensity of stimulation: 120% of the resting Motor Threshold (rMT), Frequency: 18 Hz (50% of patients) and 1 Hz (50% of patients), Duration of the train: 2 sec or 10 min, Inter-train interval: 20 sec or 1 min, Trains number: 80 or 4, Total pulses: 2880 or 2400, Total treatment duration: 29.3 or 43 min, Cue (sight of food preferred by patient): present.
intervention type: Device
intervention name: High frequency repetitive dTMS
description: Focal rTMS will be performed using a Magstim Rapid2 magnetic stimulator (The Magstim Co. Ltd., U.K.) equipped with an H-shaped coil. The used H-coil version is the H-addiction specifically designed to stimulate the insula and the Pre-Frontal Cortex (PFC). This novel H-coil allows direct stimulation of deeper brain regions, like insula (3 cm vs 1.5 cm from the skull). Before each stimulation the resting Motor Threshold (rMT) should be determined. The rMT will be determined over the left primary motor cortex, afterwards the coil will be moved forward 6 cm anterior the motor spot and aligned symmetrically over the PFC and insula. Repetitive dTMS induces long-lasting changes in neural excitability and dopamine release, specifically high-frequency rTMS (18 Hz) enhances cortical excitability.
arm group label: High frequency repetitive dTMS + Cue
arm group label: High frequency repetitive dTMS - No Cue
intervention type: Device
intervention name: Low frequency repetitive dTMS
description: Focal rTMS will be performed using a Magstim Rapid2 magnetic stimulator (The Magstim Co. Ltd., U.K.) equipped with an H-shaped coil. The used H-coil version is the H-addiction specifically designed to stimulate the insula and the Pre-Frontal Cortex (PFC). This novel H-coil allows direct stimulation of deeper brain regions, like insula (3 cm vs 1.5 cm from the skull). Before each stimulation the resting Motor Threshold (rMT) should be determined. The rMT will be determined over the left primary motor cortex, afterwards the coil will be moved forward 6 cm anterior the motor spot and aligned symmetrically over the PFC and insula. Repetitive dTMS induces long-lasting changes in neural excitability and dopamine release, specifically low-frequency rTMS (1 Hz) inhibits cortical excitability.
arm group label: Low frequency repetitive dTMS - No Cue
arm group label: Low frequency repetitive dTMS+ Cue
intervention type: Device
intervention name: Sham
description: Sham stimulation will be performed by an H-sham-coil. The H-sham-coil is designed to mimic the auditory artifacts and the scalp sensation evoked by the real coil, without stimulating the brain itself. As in the other groups, in each patient the rMT will be determined before each repetitive dTMS session. The sham stimulation will be performed either at high frequency (50% of subjects) or at low-frequency (50% of subjects), according to the previously described methodologies. All obese people in this group will be submitted at the sight of food preferred (cue).
arm group label: Sham
criteria: 
gender: All
minimum age: 22 Years
maximum age: 65 Years
healthy volunteers: No
last name: Anna Ferrulli, M.D., Ph. D.
phone: +39 3332742606
email: anna.ferrulli@grupposandonato.it
last name: Livio Luzi, Professor
phone: +39 02-52774635
email: livio.luzi@unimi.it
facility: 
status: Recruiting
contact: 
country: Italy
citation: Strafella AP, Paus T, Barrett J, Dagher A. Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci. 2001 Aug 1;21(15):RC157. doi: 10.1523/JNEUROSCI.21-15-j0003.2001.
PMID: 11459878
citation: Pascual-Leone A, Houser CM, Reese K, Shotland LI, Grafman J, Sato S, Valls-Sole J, Brasil-Neto JP, Wassermann EM, Cohen LG, et al. Safety of rapid-rate transcranial magnetic stimulation in normal volunteers. Electroencephalogr Clin Neurophysiol. 1993 Apr;89(2):120-30. doi: 10.1016/0168-5597(93)90094-6.
PMID: 7683602
citation: Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol. 1998 Jan;108(1):1-16. doi: 10.1016/s0168-5597(97)00096-8.
PMID: 9474057
citation: Zangen A, Roth Y, Voller B, Hallett M. Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil. Clin Neurophysiol. 2005 Apr;116(4):775-9. doi: 10.1016/j.clinph.2004.11.008. Epub 2004 Dec 16.
PMID: 15792886
citation: Innamorati M, Imperatori C, Balsamo M, Tamburello S, Belvederi Murri M, Contardi A, Tamburello A, Fabbricatore M. Food Cravings Questionnaire-Trait (FCQ-T) discriminates between obese and overweight patients with and without binge eating tendencies: the Italian version of the FCQ-T. J Pers Assess. 2014;96(6):632-9. doi: 10.1080/00223891.2014.909449. Epub 2014 May 2.
PMID: 24793741
citation: Uher R, Yoganathan D, Mogg A, Eranti SV, Treasure J, Campbell IC, McLoughlin DM, Schmidt U. Effect of left prefrontal repetitive transcranial magnetic stimulation on food craving. Biol Psychiatry. 2005 Nov 15;58(10):840-2. doi: 10.1016/j.biopsych.2005.05.043. Epub 2005 Aug 8.
PMID: 16084855
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.
PMID: 26110109
citation: Dinur-Klein L, Dannon P, Hadar A, Rosenberg O, Roth Y, Kotler M, Zangen A. Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: a prospective, randomized controlled trial. Biol Psychiatry. 2014 Nov 1;76(9):742-9. doi: 10.1016/j.biopsych.2014.05.020. Epub 2014 Jun 5.
PMID: 25038985
responsible party type: Principal Investigator
investigator affiliation: Ospedale San Donato
investigator full name: Anna Ferrulli
investigator title: M.D., Ph.D, Sub-Investigator
mesh term: Obesity
mesh term: Nutrition Disorders
sharing ipd: No