Transcranial Magnetic Stimulation (TMS) in Obesity

NCT03009695 | Unknown DMC

• 1 other identifier: SMT/obesi
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity; Food Craving; Appetite and General Nutritional Disorders

Keywords

Transcranial Magnetic Stimulation; Obesity; Food Craving; Appetite/Satiety Hormones; fMRI; Intestinal microbiota; Physical activity

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline and end of treatment (5 weeks)

Secondary Outcomes (19)

• Changes in body weight induced by repetitive dTMS from baseline at 5 weeks

  Baseline and end of treatment (5 weeks)

• Changes in Fat Mass (FM) rate induced by repetitive dTMS from baseline at 5 weeks

  Baseline and end of treatment (5 weeks)

• Acute and chronic changes in insulin levels induced by repetitive dTMS from baseline at 5 weeks

  Baseline and end of treatment (5 weeks)

• Acute and chronic changes in glucagon levels induced by repetitive dTMS from baseline at 5 weeks

  Baseline and end of treatment (5 weeks)

• Acute and chronic changes in ghrelin levels induced by repetitive dTMS from baseline at 5 weeks

  Baseline and end of treatment (5 weeks)

Other Outcomes (6)

• Changes in Resting Energy Expenditure (REE) induced by repetitive dTMS from baseline at 5 weeks

  Baseline and end of treatment (5 weeks)

• Changes in Activity Energy Expenditure (AEE) induced by repetitive dTMS from baseline at 5 weeks

  Baseline and end of treatment (5 weeks)

• Changes in cutaneous temperature induced by repetitive dTMS from baseline at 5 weeks

  Baseline and end of treatment (5 weeks)

Study Arms (5)

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.

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.

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

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.

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.

Device: Sham

Interventions

High frequency repetitive dTMS DEVICE

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.

High frequency repetitive dTMS + Cue; High frequency repetitive dTMS - No Cue

Low frequency repetitive dTMS DEVICE

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.

Low frequency repetitive dTMS - No Cue; Low frequency repetitive dTMS+ Cue

Sham DEVICE

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).

Sham

Eligibility Criteria

• Age: 22 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ospedale San Donato: lead

Study Sites (1)

San Donato Hospital

San Donato Milanese, MI, 20097, Italy

RECRUITING

Related Publications (10)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Ferrulli 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.

  PMID: 41451880 DERIVED

• Devoto 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.

  PMID: 33853721 DERIVED

MeSH Terms

Conditions

Obesity; Motor Activity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Central Study Contacts

Anna Ferrulli, M.D., Ph. D.

CONTACT

+39 3332742606; anna.ferrulli@grupposandonato.it

Livio Luzi, Professor

CONTACT

+39 02-52774635; livio.luzi@unimi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph.D, Sub-Investigator

Study Record Dates

• First Submitted: December 4, 2016
• First Posted: January 4, 2017
• Study Start: February 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: September 7, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)