Clinical trial NCT03336879: Repetitive Transcranial Magnetic Stimulation in Gambling Disorder
Official title: Exploring the Potential of High-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat Gambling Disorder (GD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Gambling Disorder
Keywords: Gambling Disorder
Mental Disorder
Behavioral Addiction
Lead sponsor: ITAB - Institute for Advanced Biomedical Technologies
Sponsor class: OTHER
First posted: 2017-11-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: non-randomized, open label study
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Changes in the Visual Analogue Scale for Craving (VAS-craving)
timeFrame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
measure: Changes in the Pathological Gambling Adaptation of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS)
timeFrame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
measure: Changes in Gambling Disorder Severity as assessed by Timeline Follow Back (TLFB)
timeFrame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months
measure: Changes in Gambling Behavior as assessed by Gambling Symptom Assessment Scale (G-SAS) Total Score
timeFrame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months
Secondary outcomes:
measure: Changes in the Iowa Gambling Task (IGT) Performance
timeFrame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
measure: Changes in Snaith Hamilton Pleasure Scale (SHAPS) Total Score
timeFrame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
measure: Changes in Temporal experience of Pleasure Scale (TEPS) Total
timeFrame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
measure: Changes in Montgomery-Asberg Depression Scale (MADRS) Total
timeFrame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months]
measure: Changes in Hamilton Rating Scale for Anxiety (HAM-A) Total
timeFrame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
measure: Changes in Profile of Mood States (POMS), Total Mood Disturbance Score
timeFrame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Other outcomes:
Locations:
city: Chieti
country: Italy
facility: Department of Neuroscience, Imaging and Clinical Sciences
city: Roma
country: Italy
facility: La Promessa ONLUS
Study officials:
affiliation: Department of Neuroscience, Imaging and Clinical Sciences (ITAB) - University G. d'Annunzio - Chieti (Italy)
name: Massimo di Giannantonio, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.