Clinical trial NCT05016479: Accelerated rTMS in Gambling Disorder: a Multicentric, Randomized, Sham-controlled Trial
Official title: Accelerated rTMS in Gambling Disorder: a Multicentric, Randomized, Sham-controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Gambling
Gambling Disorder
Gambling, Pathological
Gambling Problem
Keywords: arTMS
Transcranial Magnetic Stimulation
TMS
Gambling Disorder
Lead sponsor: ITAB - Institute for Advanced Biomedical Technologies
Sponsor class: OTHER
First posted: 2021-08-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blind, randomized, sham-controlled with a 1:1 allocation into 2 parallel arms
Primary purpose: TREATMENT

Brief summary: Background: Gambling disorder (GD), is a behavioral addiction based on keeping play despite medical, economic and social consequences. GD is characterized by progressive and persistent brain circuits alterations (reward, stress, memory, impulse control and cognitive functions), so a possible treatment could be based on neuromodulation of specific brain areas. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation, which provides magnetic stimuli on certain brain areas parts with short and long-term effects. rTMS has the FDA approval for some neurological (headache) and psychiatric (treatment-resistant depression, obsessive-compulsive disorder) disease. Nowadays several evidence in scientific literature lead to a promise use of rTMS also in addiction field with a possible indication also for GD.

Objectives: the main outcome is to assess symptoms related to GD (craving, play frequencies, money lost) before and after rTMS stimulation on left dorsolateral prefrontal cortex (DLPFC).

Eligibility: Healthy, right-handed adults ages 18-65 with a diagnosis of GD. Design: This is a randomized, sham-controlled study. The study includes two phases:1) a rTMS continued treatment phase and 2) a follow-up without rTMS stimulation (30 days).

In order to be enrolled, participants will be screened with:

* Questionnaires
* Medical history
* Physical exam
* f-MRI

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

* Questionnaires
* Functional MRI
* Cognitive tasks

During the continued rTMS phase, participants with gambling disorder will be randomized to receive real or sham rTMS. RTMS will be delivered during 5 outpatient treatment days, (3 times/die). After the last stimulation and at the end of the 30-days of follow-up period, subjects will undergo the neurocognitive and psychometric evaluation.

Twenty randomized patients of whole enrolled group will undergo fMRI at baseline and at the end of arTMS treatment phase.

Treatment includes:

* rTMS: A weak electrical current passes through a coil placed on the head. During each stimulation day, participants will receive three rTMS sessions (13 min), with a 50 min of interval.
* fMRI: Participants lie on a table that slides into a cylinder that takes pictures of the brain. They respond to images while in the scanner.
* Repeat of screening tests and questionnaires

Detailed description: Repetitive Transcranial Magnetic Stimulation (rTMS) is a neurostimulation technique that consists in the application of magnetic pulses in order to modulate local brain activity, opened up the possibility of interacting with dysfunctional brain circuits, selectively targeting gambling-related cognitive dysfunction.

The main outcome of the present study is to evaluate, in a population of GD patients, the effects of accelerated rTMS (arTMS) applied on Left Dorsolateral Prefrontal Cortex (LDLPFC) in terms of variations in gambling-related symptoms.

In order to investigate the possible effects of arTMS on brain connectivity, a subsample of patients will undergo a functional neuroimaging study based on fMRI.

The study includes 3 psychiatric assessments with psychometric testing: V1 (enrollment), V2 (day 5), V3 (week 4, follow-up).

At Visit 1 (enrollment) the researcher will fully inform the patient about the study, obtaining the patient's informed consent to participate in the study, and will determine the patient's eligibility. Patients will also undergo a battery of cognitive tasks and psychometric evaluation. The same neurocognitive and psychiatric assessment will be repeated during Visit 2 (day 5) and Visit 3 (4 Weeks).

The analysis of the neuroimaging data will allow to evaluate the effect of the active arTMS on brain connectivity (reward system, attention and executive control networks) investigate the association between these evidence and clinical variables.

Eligibility criteria: Inclusion Criteria:

* Current diagnosis of Gambling Disorder, based on the Diagnostic and Statistical Manual of Mental Disorder - Fifth Edition (DSM-5);

Exclusion Criteria:

* Current or pre-existing DSM-5 diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder;
* Use in the past 4 weeks of any medication with known pro-convulsant action, including antipsychotic medications, tricyclic antidepressants, and antihistamines drugs;
* Medical history with significant neurological disorder, including organic brain disease, epilepsy, stroke, brain lesions and 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, according to 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: Change in gambling behavior assessed by Yale Brown Obsessive Compulsive Scale adapted for Pathological Gambling (PG-YBOCS)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in gambling behavior assessed by Gambling Symptom Assessment Scale (G-SAS)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in gambling behavior assessed by TimeLine Follow Back (TLFB) - Gambling Version
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in gambling behavior assessed by Visual Analogue Scale
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
Secondary outcomes:
measure: Change in attention / hyperactivity symptoms assessed by Adult ADHD Self-Report Scale (ASRS)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in emotional awareness assessed by Toronto Alexithymia Scale (TAS-20)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in mood state assessed by Profile of Mood States (POMS)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in search for sensations assessed by Sensation Seeking Scale V (SSS-V)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in hedonic tone assessed by Snaith-Hamilton Pleasure Scale (SHAPS)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in hedonic tone assessed by Temporal Experience of Pleasure Scale (TEPS)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in quality of life assessed by Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in suicidal behaviours assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in psychopathological symptoms assessed by SCL-90
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in food craving assessed by Food craving questionnaire (FCI)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in sleep quality assessed by Insomnia severity index (ISI)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in nicotine craving assessed by Short Tobacco Craving Questionnaire (sTCQ)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in anxiety level assessed by Hamilton Anxiety Scale (HAM-A)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in depressive symptoms assessed by Hamilton Depression Scale (HAM-D)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in manic symptoms assessed by Young Mania Rating Scale (YMRS)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in positive and negative symptoms assessed by Positive Affect and Negative Affect Scales (PANAS)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in impulsivness assessed by Barratt Impulsiveness Scale (BIS-11)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in cognitive performance by Iowa gambling task (IGT)
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in cognitive performance by Go / No-Go Task
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in cognitive performance by Stroop color-word task
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
measure: Change in cognitive performance by Wisconsin card-sorting task
timeFrame: Baseline, after rTMS treatment (5 day), 4 weeks
Other outcomes:
Locations:
Study officials:
affiliation: ITAB - Institute for Advanced Biomedical
name: Massimo di Giannantonio, MD
role: PRINCIPAL_INVESTIGATOR
References: