ObesityNCT03009695
Transcranial Magnetic Stimulation (TMS) in Obesity
A study testing High frequency repetitive dTMS and Low frequency repetitive dTMS in people with Obesity and Food Craving, run by Ospedale San Donato at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 to 65 years
- Conditions the study is for
- Obesity, Food Craving, Appetite and General Nutritional Disorders
- What is being tested?
- High frequency repetitive dTMS and Low frequency repetitive dTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2015to Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
San Donato Hospital
San Donato Milanese, MI, 20097
Anna Ferrulli, MD, anna.ferrulli@grupposandonato.it
About this study
Official title: Impact of Deep Transcranial Magnetic Stimulation (dTMS) on Satiety and Weight Control
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.
- Being tested
- High frequency repetitive dTMS, Low frequency repetitive dTMS, Sham
- Keywords
- Transcranial Magnetic Stimulation, Obesity, Food Craving, Appetite/Satiety Hormones, fMRI, Intestinal microbiota, Physical activity
- Medical subject headings
- Obesity, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High frequency repetitive dTMSDevice
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.
Low frequency repetitive dTMSDevice
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.
ShamDevice
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).
| Study group | Role | What they receive |
|---|---|---|
| High frequency repetitive dTMS + Cue | Experimental | 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. Receives: Device: High frequency repetitive dTMS |
| High frequency repetitive dTMS - No Cue | Experimental | 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. Receives: Device: High frequency repetitive dTMS |
| Low frequency repetitive dTMS+ Cue | Experimental | 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 Receives: Device: Low frequency repetitive dTMS |
| Low frequency repetitive dTMS - No Cue | Experimental | 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. Receives: Device: Low frequency repetitive dTMS |
| Sham | Sham comparator | 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. Receives: Device: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and end of treatment (5 weeks)
Secondary outcomes (19)
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.
Measured: Baseline and end of treatment (5 weeks)
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
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
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).
Measured: Baseline and end of treatment (5 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2017 (estimated)
- Study startFeb 2015
- Primary completionDec 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ospedale San Donato
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anna Ferrulli, Ospedale San Donato
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03009695
- Sponsor's protocol ID
- SMT/obesi
- Status last verified
- Sep 2018
- First submitted
- 4 Dec 2016
- Last updated
- 7 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 11459878Pascual-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.
PubMed 7683602Wassermann 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.
PubMed 9474057Zangen 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.
PubMed 15792886Innamorati 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.
PubMed 24793741Uher 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.
PubMed 16084855Val-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.
PubMed 26110109Dinur-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.
PubMed 25038985Ferrulli A, Senesi P, Sonaglioni A, Cannavaro D, Massarini S, Macri C, Cipponeri E, DeFronzo RA, Luzi L. Weight Loss With SGLT2 Inhibitors, Semaglutide, and Transcranial Magnetic Stimulation in Type 2 Diabetes and Obesity. Obesity (Silver Spring). 2026 Feb;34(2):317-322. doi: 10.1002/oby.70105. Epub 2025 Dec 26.
PubMed 41451880Devoto F, Ferrulli A, Zapparoli L, Massarini S, Banfi G, Paulesu E, Luzi L. Repetitive deep TMS for the reduction of body weight: Bimodal effect on the functional brain connectivity in "diabesity". Nutr Metab Cardiovasc Dis. 2021 Jun 7;31(6):1860-1870. doi: 10.1016/j.numecd.2021.02.015. Epub 2021 Feb 25.
PubMed 33853721
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Deep Transcranial Magnetic Stimulation (dTMS) on Satiety and Weight Control
- ClinicalTrials.gov ID
- NCT03009695
- Acronym / sponsor ID
- SMT/obesi
- Keywords
- Transcranial Magnetic Stimulation, Obesity, Food Craving, Appetite/Satiety Hormones, fMRI, Intestinal microbiota, Physical activity
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Ospedale San DonatoUniversity, hospital or other
- Study start
- Feb 2015
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 4 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| High frequency repetitive dTMS + Cue | Experimental | Device: High frequency repetitive dTMS10 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. |
| High frequency repetitive dTMS - No Cue | Experimental | Device: High frequency repetitive dTMS10 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. |
| Low frequency repetitive dTMS+ Cue | Experimental | Device: Low frequency repetitive dTMS10 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 |
| Low frequency repetitive dTMS - No Cue | Experimental | Device: Low frequency repetitive dTMS10 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. |
| Sham | Sham comparator | Device: Sham10 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. |
Who may qualify
- Ages
- 22 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High frequency repetitive dTMSFocal 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. | Device | High frequency repetitive dTMS + Cue, High frequency repetitive dTMS - No Cue |
| Low frequency repetitive dTMSFocal 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. | Device | Low frequency repetitive dTMS - No Cue, Low frequency repetitive dTMS+ Cue |
| ShamSham 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). | Device | Sham |
Primary outcome
Changes in food craving levels induced by repetitive dTMS from baseline at 5 weeks
Time frame: Baseline and end of treatment (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).
19 secondary outcomes
Changes in body weight induced by repetitive dTMS from baseline at 5 weeks
Time frame: Baseline and end of treatment (5 weeks)
Changes in Fat Mass (FM) rate induced by repetitive dTMS from baseline at 5 weeks
Time frame: Baseline and end of treatment (5 weeks)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Changes in Beta-endorphin levels induced by repetitive dTMS from baseline at 5 weeks
Time frame: Baseline and end of treatment (5 weeks)
Changes in Epinephrine levels induced by repetitive dTMS from baseline at 5 weeks
Time frame: Baseline and end of treatment (5 weeks)
Changes in Norepinephrine levels induced by repetitive dTMS from baseline at 5 weeks
Time frame: Baseline and end of treatment (5 weeks)
Changes in Glucose levels induced by repetitive dTMS from baseline at 5 weeks
Time frame: Baseline and end of treatment (5 weeks)
Changes in Glycated Hemoglobin levels induced by repetitive dTMS from baseline at 5 weeks
Time frame: Baseline and end of treatment (5 weeks)
Changes in Cholesterol levels induced by repetitive dTMS from baseline at 5 weeks
Time frame: Baseline and end of treatment (5 weeks)
Changes in Triglyceride levels induced by repetitive dTMS from baseline at 5 weeks
Time frame: Baseline and end of treatment (5 weeks)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2018.
- Background: PubMed 11459878Strafella 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.
- Background: PubMed 7683602Pascual-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.
- Background: PubMed 9474057Wassermann 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.
- Background: PubMed 15792886Zangen 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.
- Background: PubMed 24793741Innamorati 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.
- Background: PubMed 16084855Uher 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.
- Background: PubMed 26110109Val-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.
- Background: PubMed 25038985Dinur-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.
- Derived from this study: PubMed 41451880Ferrulli A, Senesi P, Sonaglioni A, Cannavaro D, Massarini S, Macri C, Cipponeri E, DeFronzo RA, Luzi L. Weight Loss With SGLT2 Inhibitors, Semaglutide, and Transcranial Magnetic Stimulation in Type 2 Diabetes and Obesity. Obesity (Silver Spring). 2026 Feb;34(2):317-322. doi: 10.1002/oby.70105. Epub 2025 Dec 26.
- Derived from this study: PubMed 33853721Devoto F, Ferrulli A, Zapparoli L, Massarini S, Banfi G, Paulesu E, Luzi L. Repetitive deep TMS for the reduction of body weight: Bimodal effect on the functional brain connectivity in "diabesity". Nutr Metab Cardiovasc Dis. 2021 Jun 7;31(6):1860-1870. doi: 10.1016/j.numecd.2021.02.015. Epub 2021 Feb 25.
- Individual participant dataSharing planned: No
Related trials for Obesity
Not yet recruiting
Transcutaneous Auricular Vagus Nerve Stimulation Combined With Lifestyle Intervention for Visceral Fat Reduction in Adults With Overweight or Obesity
Overweight, Obesity
Not yet recruitingObservational study
Assessing the Impact of Perceptions of Unpredictability on Objective Measures of Food Consumption and Metabolism
Healthy Volunteer, Obestity
RecruitingPhase 1/2
HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
Pulmonary Hypertension, Heart Failure With Preserved Ejection Fraction
Not yet recruitingPhase 3
ELEVATE-LIVER: A Study to Test Whether Survodutide Helps Improve Heart Structure and Function in People With Overweight or Obesity and Fatty Liver Disease
Obesity, Metabolic Dysfunction-associated Steatotic Liver Disease
Not yet recruitingObservational study
A Natural History of Genetic and Environmental Predictors of Pubertal Timing Among Youth With Obesity
Obesity
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High frequency repetitive dTMS and Low frequency repetitive dTMS in people with Obesity and Food Craving, run by Ospedale San Donato at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anna Ferrulli, M.D., Ph. D. (+39 3332742606, anna.ferrulli@grupposandonato.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in food craving levels induced by repetitive dTMS from baseline at 5 weeks (time frame: Baseline and end of treatment (5 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03009695, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2018.