Repetitive Transcranial Magnetic Stimulation in Gambling Disorder

NCT ID: NCT03336879

Last Updated: 2017-11-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-01
• Study Completion Date: 2020-12-30

Brief Summary

Background: An imbalance between prefrontal cortex (PFC) and the mesolimbic reward system has been suggested to contribute to GD. GD patients showed increased functional connectivity between regions of the PFC and mesolimbic reward system, as well as reduced connectivity in the area of the PFC. The altered interaction between prefrontal structures and the mesolimbic reward system in GD shares similarity with functional organization reported in Substances Use Disorders (SUDs), suggesting a more general pathophysiology for addictive disorders

Objectives: To test if rTMS can reduce craving and playing in Gambling Disorder, and also affect several mood, behavioral and cognitive alterations associated with prolonged Gambling Disorder.

Eligibility: Healthy, right-handed adults ages 18-65 who do have Gambling Disorder.

Design: This is a non-randomized, open label study. The study includes three phases: 1) a rTMS continued treatment phase; 2) a rTMS follow-up; and 3) a no rTMS follow-up.

Prior to participating, participants will be screened with:

• Questionnaires
• Cognitive tests
• Medical history
• Physical exam

After being enrolled, baseline behavioral and imaging data will be collected. In particular, participants will undergo:

• Questionnaires
• Cognitive tests

During the continued rTMS phase, participants with Gambling Disorder will receive real rTMS. Repetitive TMS will be delivered during 10 outpatient treatment days, over 2 weeks (5 days/week). Following this phase, subjects will have 12 follow-up visits (once/weekly), during which they will receive rTMS, and behavioral assessments will be performed. At the end of the rTMS follow up period, participants will further receive 3 follow up visits (once a month), during which rTMS will not be performed, but behavioral data will be collected.

Treatment includes:

• rTMS: A coil is placed on the head. Brief electrical current passes through the coil. At each visit, participants will receive two rTMS sessions, with a 1hr interval between sessions. At the beginning of each rTMS session, they view gambling-related images for few minutes.
• Repeat of screening tests and questionnaires

Detailed Description

Gambling Disorder (GD) is a complex addictive disorder involving fronto-striatal connectivity and prefrontal top-down control modulation of reward-related brain areas. Repetitive transcranial magnetic stimulation (rTMS) seems to reduce cravings and improve cognitive function in substance dependent individuals. Moreover, rTMS has been shown to modulate dopaminergic and glutamatergic transmission, both involved in GD pathophysiology. However, the efficacy of rTMS in treating GD has not been evaluated and also, we lack a full characterization of rTMS effects on other important aspects, including effects on mood, cognition and changes in brain function. The purpose of this study is to investigate the effects of repetitive Transcranial Magnetic Stimulation (rTMS) at 15 Hz frequency on the left dorsolateral prefrontal cortex in patients affected by GD and to examine possible changes in mood, cognition, and brain activity and functional connectivity associated with this intervention. For this purpose, the investigators will recruit GD patients. After screening and informed consent, participants will undergo active rTMS for two consecutive weeks (twice a day) during the continued treatment phase, and a maintenance intervention (twice a week for 3 months), during the rTMS follow-up phase. Following this phase, participants will be followed for further 3 months, during which no rTMS will be delivered but clinical data will be collected.

Procedure: The project consists of: Screening Visit (baseline), Phase 1 (continued treatment phase), Phase 2 (3 months- rTMS follow-up), Phase 3 (3 months follow-up without rTMS). First, there will be a screening visit, where a clinical interview will be conducted and questionnaires and tests will be administered to identify study participants who meet the inclusion and exclusion criteria. Baseline clinical and cognitive data will be acquired. In Phase 1, participants will receive 2 sessions of rTMS (active), twice per day for 10 consecutive days, for a total of 20 rTMS sessions. Following this, the investigators will evaluate the acute effect of treatment on relapse rate, gambling severity and craving, mood and cognition. In Phase 2 of the study, all participants will continue the treatment arm with rTMS (15Hz) for three months. Participants will receive 2 sessions of rTMS (active) once per week; clinical and cognitive data will be acquired once per month. The investigators will evaluate the acute effect of treatment on relapse rate, gambling severity and craving, mood and cognition. In Phase 3 of the study, participants will not receive any rTMS session. Clinical and cognitive data will be acquired once per month for three months. The investigators will evaluate the long-term effect of treatment on relapse rate, gambling severity and craving, mood and cognition.

Conditions

Gambling Disorder

Keywords

Gambling Disorder; Mental Disorder; Behavioral Addiction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Active rTMS (15 Hz)

The intervention will be Repetitive Transcranial Magnetic Stimulation. Each patient will receive active stimulation targeting the left dorsolateral prefrontal cortex (lDLPFC) with a frequency of 15 Hz and 100% of the individual resting motor threshold, for a total of 40 trains (60 stimuli per train, inter-train interval of 15 second, total duration 13 minutes). Each session will be repeated twice/daily for 10 consecutive days for 2 weeks, during the continued treatment phase. Following this, the participants will receive the maintenance intervention of 2 sessions per week for 3 months (rTMS follow-up), at the same parameters described above. Device: MagPro R30 with the Cool-B80 figure-of-eight coil (MagVenture, Falun, Denmark).

Group Type: EXPERIMENTAL

Repetitive Transcranial Magnetic Stimulation

Intervention Type: DEVICE

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique. The investigators will use a MagPro R30 with the Cool-B80 figure-of-eight coil (MagVenture, Falun, Denmark).

Interventions

Repetitive Transcranial Magnetic Stimulation

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique. The investigators will use a MagPro R30 with the Cool-B80 figure-of-eight coil (MagVenture, Falun, Denmark).

Intervention Type: DEVICE

Other Intervention Names

rTMS

Eligibility Criteria

Inclusion Criteria

• Age 18 - 65;
• Current diagnosis of Gambling Disorder, based on the Diagnostic and Statistical Manual of Mental Disorder - Fifth Edition (DSM-5);
• Drug-free.

Exclusion Criteria

• Current DSM-V diagnosis of substance use disorders other than nicotine dependence;
• Current DSM-V diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder;
• Use in the past 4 weeks of any medication with known pro-convulsant action; or current regular use of any psychotropic medications (benzodiazepines, antipsychotic medications, tricyclic antidepressants, anti-epileptics, mood stabilizers);
• Any history of any clinically significant neurological disorder, including organic brain disease, epilepsy, stroke, brain lesions, multiple sclerosis, previous neurosurgery, or personal history of head trauma that resulted in loss of consciousness for > 5 minutes and retrograde amnesia for > 30 minutes;
• Any personal or family history (1st degree relatives) of seizures other than febrile childhood seizures;
• Any psychiatric, medical or social condition whether or not listed above, due to which, in the judgment of the PI and after any consults if indicated, participation in the study is not in the best interest of the patient;
• For female patients: Pregnancy/breastfeeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ITAB - Institute for Advanced Biomedical Technologies

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Martinotti

Researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Massimo di Giannantonio, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neuroscience, Imaging and Clinical Sciences (ITAB) - University G. d'Annunzio - Chieti (Italy)

Locations

Department of Neuroscience, Imaging and Clinical Sciences

Chieti, , Italy

Site Status: RECRUITING

La Promessa ONLUS

Roma, , Italy

Site Status: NOT_YET_RECRUITING

Countries

Italy

Central Contacts

Giovanni Martinotti, MD, PhD

Role: CONTACT

Phone: 0039 0871 3556914

Email: giovanni.martinotti@gmail.com

Mauro Pettorruso, MD

Role: CONTACT

Phone: 0039 3391979487

Email: mauro.pettorruso@hotmail.it

Facility Contacts

Givoanni Martinotti, MD, PhD

Role: primary

Chiara Montemitro, MD

Role: backup

Mauro Pettorruso, MD

Role: primary

References

Pettorruso M, Martinotti G, Montemitro C, De Risio L, Spagnolo PA, Gallimberti L, Fanella F, Bonci A, Di Giannantonio M; Brainswitch Study Group. Multiple Sessions of High-Frequency Repetitive Transcranial Magnetic Stimulation as a Potential Treatment for Gambling Addiction: A 3-Month, Feasibility Study. Eur Addict Res. 2020;26(1):52-56. doi: 10.1159/000504169. Epub 2019 Oct 30.

Reference Type: DERIVED

PMID: 31665732 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

v.2_19/10/2017

Identifier Type: -

Identifier Source: org_study_id