Effects of Frontopolar TMS in Alcohol Craving (TMS-SUD)

Goethe University

Status: Enrolling

Conditions: Alcohol Addiction

Treatments: Device: Transcranial Magnetic Stimulation (TMS)

Study type: Interventional

Funder types: Other

Identifiers

NCT07064590

2024-2021

Details and patient eligibility

About

The goal of this interventional study is to learn if continuous theta burst stimulation (cTBS) applied over the left frontopolar cortex can reduce psychological, physiological, and neurobiological markers of alcohol craving in patients with alcohol dependence (AD).

The main questions it aims to answer are:

• Does cTBS over the left frontopolar cortex reduce psychological and physiological measures of alcohol craving in individuals with AD?
• Are baseline structural and functional brain connectivity patterns associated with individual differences in cTBS-induced changes in craving?

The participants will:

• Receive cTBS over the left frontopolar cortex using an accelerated protocol comprising 15 TMS-sessions on five consecutive days
• Undergo psychological and physiological assessments of alcohol craving before and after the TMS intervention
• Complete magnetic resonance imaging (MRI) sessions to assess baseline brain structural and functional connectivity

This study aims to advance the understanding of the neurophysiological mechanisms underlying craving in AD and the identification of potential biomarkers for predicting psychological and physiological craving reductions.

Full description

Alcohol dependence (AD) is a prevalent and debilitating condition characterized by a chronic inability to control alcohol consumption despite adverse consequences. Current treatment options have limited efficacy, highlighting the pressing need for innovative approaches. Continuous Theta Burst Stimulation (cTBS) is a form of transcranial magnetic stimulation (TMS) that has shown promise in modulating brain activity associated with craving and addiction.

This study aims to explore the effects of cTBS applied over the left frontopolar cortex on psychological, physiological, and neurobiological markers of alcohol craving in patients with AD. Specifically, this study will assess TMS-induced changes in psychological alcohol craving using the Penn Alcohol Craving Scale (PACS), and physiological alcohol craving using physiological craving markers, including heart rate (HR), skin temperature (ST) and skin conductance (SC), and their changes during Virtual Reality Cue Exposure and Craving Assessment (VR-CECA) before and after the TMS intervention. Additionally, the study aims to explore the relationship between neurobiological craving markers utilizing baseline structural and functional brain connectivity as assessed by magnetic resonance imaging (MRI) and TMS-induced changes in psychological and physiological alcohol craving.

This study aims to include a total of 34 patients aged 18-65 years with an ICD-10 diagnosis of AD. All participants undergo 15 sessions of accelerated cTBS targeting the left frontopolar cortex over five consecutive days using neuronavigation based on individual MRI scans. Clinical (questionnaires, diagnostic interviews) and behavioural (VR-CECA) assessments are conducted at two time points: pre-TMS intervention and post-TMS intervention. Structural and functional MRI scans are acquired before the TMS intervention to assess individual brain connectivity.

The primary outcome will be the TMS-induced change in psychological alcohol craving assessed with the PACS. Secondary outcomes include TMS-induced changes in physiological craving markers (HR, ST, and SC) during VR-CECA and TMS-induced changes and psychopathological states that will be assessed through a battery of clinical questionnaires.

This study hypothesizes that frontopolar cTBS will reduce psychological and physiological alcohol craving in patients with AD. Additionally, this study expects that baseline structural and functional connectivity will predict TMS-induced changes in physiological alcohol craving, providing insights into individual brain network variability on the effect of frontopolar cTBS.

This study aims to advance the understanding of the neurophysiological mechanisms underlying craving in AD and the identification of potential biomarkers for predicting psychological and physiological craving reductions. If successful, this could lead to more targeted and effective interventions for AD, ultimately improving patient outcomes.

Enrollment: 34 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• adults aged 18-65
• ICD-10 diagnosis of alcohol dependence
• Ability to give consent
• Sinus rhythm in ECG

Exclusion criteria

• Current psychotic symptoms in patients with psychotic disorders (F20, F23, F10.5)
• Contraindication against TMS or MRI
• Severe neurological disorders such as epilepsy, stroke, neuroinflammatory disorders (e.g., multiple sclerosis). A history of seizures only in the context of alcohol withdrawal does not represent a contraindication, unless the seizure happened in the last 3 weeks before study inclusion.
• Acute withdrawal symptoms (CIWA-Ar > 5)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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34 participants in 1 patient group

Frontopolar cTBS Intervention

Experimental group

Description:

Participants in this arm will receive 15 sessions of continuous theta burst stimulation (cTBS) over the left frontopolar cortex across 5 consecutive days (3 sessions/day) using neuronavigation based on individual MRI. The stimulation intensity is set at 110% of the resting motor threshold. Virtual Reality Cue Exposure and Craving Assessment (VR-CECA) and psychological craving assessment will be performed before and after the TMS intervention. Baseline structural and functional MRI scans will be acquired before stimulation for brain connectivity analysis.

Treatment:

Device: Transcranial Magnetic Stimulation (TMS)