Back to resultsTranscranial Magnetic Stimulation (TMS) in Obesity
Primary Purpose
Obesity, Food Craving, Appetite and General Nutritional Disorders
Status
Unknown status
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
High frequency repetitive dTMS
Low frequency repetitive dTMS
Sham
Sponsored by
About this trial
This is an interventional treatment trial for Obesity focused on measuring Transcranial Magnetic Stimulation, Obesity, Food Craving, Appetite/Satiety Hormones, fMRI, Intestinal microbiota, Physical activity
Eligibility Criteria
Inclusion Criteria:
- Age: 22-65 years
- If the patient is taking medications, it must take on a stable dose for at least a month
- Obesity: ≤ 30 BMI ≤ 45
- Ability to follow verbal or written instructions.
Exclusion Criteria:
- Axis-I and II psychiatric disorders according to DSM criteria 5 (such as Major Depression, Bipolar Disorder, or Attention Deficit Disorder)
- IQ score < 85
- Organic brain disorders: history of stroke, brain major surgery or head trauma
- Pregnancy or lactation, absence of medically approved contraceptive methods in females of childbearing potential
- Serious or poorly controlled diseases (hepatic, renal or hearth failure, atrial fibrillation or other heart rhythm disorders)
- H yperglycemia - Fasting glucose level > 170 mg/dl
- Urine drug screen positive for amphetamines, barbiturates, cannabinoids, cocaine metabolites, opiates and phencyclidine
- Positivity to blood alcohol test
- Metal in any part of the head, except for dental fillings
- Implanted infusion pumps
- Intracardiac devices (pacemakers, heart valves ...)
- History of diseases whose exacerbation could be fatal (e.g. cardiovascular disease, increased intracranial pressure)
- History of epilepsy or a family history of epilepsy among first-degree relatives
- Medications associated with lowered seizure threshold (such as antidepressants, anxiolytics…)
- Treatment with anti-obesity medications or other medications influencing body weight within 3 month prior to Screening Visit
- Starting a weight loss plan at any time during data collection for the subject
- Patients affected by galactosemia, priapism and terminal illness
- Patients on fluid restriction for SIADH or other conditions
- Contraindications to perform the Magnetic Resonance Imaging (MRI).
Sites / Locations
- San Donato HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Sham Comparator
Arm Label
High frequency repetitive dTMS + Cue
High frequency repetitive dTMS - No Cue
Low frequency repetitive dTMS+ Cue
Low frequency repetitive dTMS - No Cue
Sham
Arm 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.
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.
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
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.
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.
Outcomes
Primary Outcome Measures
Changes in food craving levels induced by repetitive dTMS from baseline at 5 weeks
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).
Secondary Outcome Measures
Changes in body weight induced by repetitive dTMS from baseline at 5 weeks
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.
Changes in Fat Mass (FM) rate induced by repetitive dTMS from baseline at 5 weeks
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
Acute and chronic changes in insulin levels induced by repetitive dTMS from baseline at 5 weeks
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).
Acute and chronic changes in glucagon levels induced by repetitive dTMS from baseline at 5 weeks
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).
Acute and chronic changes in ghrelin levels induced by repetitive dTMS from baseline at 5 weeks
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).
Acute and chronic changes in leptin levels induced by repetitive dTMS from baseline at 5 weeks
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).
Acute and chronic changes in Growth Hormone (GH) levels induced by repetitive dTMS from baseline at 5 weeks
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).
Acute and chronic changes in Adreno-Cortico-Tropic Hormone (ACTH) levels induced by repetitive dTMS from baseline at 5 weeks
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).
Acute and chronic changes in Thyroid-Stimulating Hormone (TSH) levels induced by repetitive dTMS from baseline at 5 weeks
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).
Acute and chronic changes in Prolactin levels induced by repetitive dTMS from baseline at 5 weeks
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).
Acute and chronic changes in Cortisol levels induced by repetitive dTMS from baseline at 5 weeks
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).
Acute and chronic changes in Neuropeptide Y levels induced by repetitive dTMS from baseline at 5 weeks
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).
Changes in Beta-endorphin levels induced by repetitive dTMS from baseline at 5 weeks
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).
Changes in Epinephrine levels induced by repetitive dTMS from baseline at 5 weeks
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).
Changes in Norepinephrine levels induced by repetitive dTMS from baseline at 5 weeks
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).
Changes in Glucose levels induced by repetitive dTMS from baseline at 5 weeks
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).
Changes in Glycated Hemoglobin levels induced by repetitive dTMS from baseline at 5 weeks
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).
Changes in Cholesterol levels induced by repetitive dTMS from baseline at 5 weeks
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).
Changes in Triglyceride levels induced by repetitive dTMS from baseline at 5 weeks
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).
Full Information
NCT ID
NCT03009695
First Posted
December 4, 2016
Last Updated
September 6, 2018
Sponsor
Ospedale San Donato
1. Study Identification
Unique Protocol Identification Number
NCT03009695
Brief Title
Transcranial Magnetic Stimulation (TMS) in Obesity
Official Title
Impact of Deep Transcranial Magnetic Stimulation (dTMS) on Satiety and Weight Control
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Unknown status
Study Start Date
February 2015 (undefined)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
December 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ospedale San Donato
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Food Craving, Appetite and General Nutritional Disorders
Keywords
Transcranial Magnetic Stimulation, Obesity, Food Craving, Appetite/Satiety Hormones, fMRI, Intestinal microbiota, Physical activity
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
High frequency repetitive dTMS + Cue
Arm Type
Experimental
Arm 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 Title
High frequency repetitive dTMS - No Cue
Arm Type
Experimental
Arm 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 Title
Low frequency repetitive dTMS+ Cue
Arm Type
Experimental
Arm 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 Title
Low frequency repetitive dTMS - No Cue
Arm Type
Experimental
Arm 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 Title
Sham
Arm Type
Sham Comparator
Arm 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(s)
High frequency repetitive dTMS
Intervention 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.
Intervention Type
Device
Intervention Name(s)
Low frequency repetitive dTMS
Intervention 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.
Intervention Type
Device
Intervention Name(s)
Sham
Intervention 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).
Primary Outcome Measure Information:
Title
Changes in food craving levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Secondary Outcome Measure Information:
Title
Changes in body weight induced by repetitive dTMS from baseline at 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.
Time Frame
Baseline and end of treatment (5 weeks)
Title
Changes in Fat Mass (FM) rate induced by repetitive dTMS from baseline at 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
Time Frame
Baseline and end of treatment (5 weeks)
Title
Acute and chronic changes in insulin levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Acute and chronic changes in glucagon levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Acute and chronic changes in ghrelin levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Acute and chronic changes in leptin levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Acute and chronic changes in Growth Hormone (GH) levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Acute and chronic changes in Adreno-Cortico-Tropic Hormone (ACTH) levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Acute and chronic changes in Thyroid-Stimulating Hormone (TSH) levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Acute and chronic changes in Prolactin levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Acute and chronic changes in Cortisol levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Acute and chronic changes in Neuropeptide Y levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Changes in Beta-endorphin levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Changes in Epinephrine levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Changes in Norepinephrine levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Changes in Glucose levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Changes in Glycated Hemoglobin levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Changes in Cholesterol levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Title
Changes in Triglyceride levels induced by repetitive dTMS from baseline at 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).
Time Frame
Baseline and end of treatment (5 weeks)
Other Pre-specified Outcome Measures:
Title
Changes in Resting Energy Expenditure (REE) induced by repetitive dTMS from baseline at 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.
Time Frame
Baseline and end of treatment (5 weeks)
Title
Changes in Activity Energy Expenditure (AEE) induced by repetitive dTMS from baseline at 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
Time Frame
Baseline and end of treatment (5 weeks)
Title
Changes in cutaneous temperature induced by repetitive dTMS from baseline at 5 weeks
Description
Abdomen and nail bed of both hands temperature (°C) will be detected by infrared thermography
Time Frame
Baseline and end of treatment (5 weeks)
Title
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
Description
Cue-induced activation of specific brain areas will be evaluated by functional Magnetic Resonance Imaging (fMRI)
Time Frame
Baseline and end of treatment (5 weeks)
Title
Assessment of adverse events
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.
Time Frame
Through study completion, an average of 1 year
Title
Changes in gut microbiota composition induced by repetitive dTMS from baseline at 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.
Time Frame
Baseline and end of treatment (5 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
22 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age: 22-65 years
If the patient is taking medications, it must take on a stable dose for at least a month
Obesity: ≤ 30 BMI ≤ 45
Ability to follow verbal or written instructions.
Exclusion Criteria:
Axis-I and II psychiatric disorders according to DSM criteria 5 (such as Major Depression, Bipolar Disorder, or Attention Deficit Disorder)
IQ score < 85
Organic brain disorders: history of stroke, brain major surgery or head trauma
Pregnancy or lactation, absence of medically approved contraceptive methods in females of childbearing potential
Serious or poorly controlled diseases (hepatic, renal or hearth failure, atrial fibrillation or other heart rhythm disorders)
H yperglycemia - Fasting glucose level > 170 mg/dl
Urine drug screen positive for amphetamines, barbiturates, cannabinoids, cocaine metabolites, opiates and phencyclidine
Positivity to blood alcohol test
Metal in any part of the head, except for dental fillings
Implanted infusion pumps
Intracardiac devices (pacemakers, heart valves ...)
History of diseases whose exacerbation could be fatal (e.g. cardiovascular disease, increased intracranial pressure)
History of epilepsy or a family history of epilepsy among first-degree relatives
Medications associated with lowered seizure threshold (such as antidepressants, anxiolytics…)
Treatment with anti-obesity medications or other medications influencing body weight within 3 month prior to Screening Visit
Starting a weight loss plan at any time during data collection for the subject
Patients affected by galactosemia, priapism and terminal illness
Patients on fluid restriction for SIADH or other conditions
Contraindications to perform the Magnetic Resonance Imaging (MRI).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Ferrulli, M.D., Ph. D.
Phone
+39 3332742606
Email
anna.ferrulli@grupposandonato.it
First Name & Middle Initial & Last Name or Official Title & Degree
Livio Luzi, Professor
Phone
+39 02-52774635
Email
livio.luzi@unimi.it
Facility Information:
Facility Name
San Donato Hospital
City
San Donato Milanese
State/Province
MI
ZIP/Postal Code
20097
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Ferrulli, MD
Email
anna.ferrulli@grupposandonato.it
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
11459878
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.
Results Reference
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PubMed Identifier
7683602
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.
Results Reference
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PubMed Identifier
9474057
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.
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PubMed Identifier
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Citation
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PubMed Identifier
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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.
Results Reference
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PubMed Identifier
16084855
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.
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PubMed Identifier
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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.
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PubMed Identifier
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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.
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PubMed Identifier
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Citation
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Results Reference
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Transcranial Magnetic Stimulation (TMS) in Obesity
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