Effects of Frontopolar TMS in Alcohol Craving

NCT07064590 | Recruiting

• 1 other identifier: 2024-2021
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Alcohol Addiction

Keywords

frontopolar transcranial magnetic stimulation (TMS); craving; alcohol addiction; addiction treatment; virtual reality (VR); magnetic resonance imaging (MRI); Continuous Theta Burst Stimulation (cTBS); neuromodulation; structural and functional brain connectivity; connectome; neurophysiological craving markers; prediction; physiological craving markers; psychological craving markers; Neuronavigation

Outcome Measures

Primary Outcomes (1)

• TMS-induced changes in psychological alcohol craving assessed with the Penn Alcohol Craving Scale (PACS)

  The primary outcome measure is the TMS-induced changes in psychological craving intensity. Self-reported psychological alcohol craving as measured by the Penn Alcohol Craving Scale (PACS) will be assessed before the frontopolar TMS intervention (pre-TMS at baseline) and after the final frontopolar TMS session (post-TMS). The PACS is a five-item, self-report measure that includes questions about the frequency, intensity, and duration of craving, the ability to resist drinking, and asks for an overall rating of craving for alcohol for the previous week. Each question is scored on a scale of 0 to 6. The mean total score across the five items (range 0-6) will be calculated, with higher scores indicating greater craving. In exploratory analyses, individual PACS items can also be examined separately to capture distinct dimensions of craving (e.g., frequency, intensity, or duration).

  The PACS will be assessed at baseline before the start of the TMS Intervention (Pre-TMS, Day 0) and after the final TMS session (post-TMS, Day 5)

Secondary Outcomes (8)

• TMS-induced change in heart rate (BPM) during virtual reality alcohol cue exposure

  HR is continuously recorded during VR alcohol cue exposure sessions conducted on Day 1 (prior to the first TMS session) and Day 5 (following the final TMS session), allowing assessment of TMS-induced changes in physiological craving response.

• TMS-induced change in skin conductance (µS) during Virtual reality alcohol cue exposure

  SC is continuously recorded during VR alcohol cue exposure sessions conducted on Day 1 (prior to the first TMS session) and Day 5 (following the final TMS session), allowing assessment of TMS-induced changes in physiological craving response.

• TMS-induced change in skin temperature (°C) during Virtual reality alcohol cue exposure

  ST is continuously recorded during VR alcohol cue exposure sessions conducted on Day 1 (prior to the first TMS session) and Day 5 (following the final TMS session), allowing assessment of TMS-induced changes in physiological craving response.

• TMS-induced change in self-reported craving during VR exposure using Visual Analogue Scale (VAS)

  Day 1 (pre-TMS; pre-VR and post-VR) and Day 5 (post-TMS; pre-VR and post-VR)

• TMS-induced change in self-reported craving assessed with the Mannheimer Craving Scale (MaCS)

  The MaCS will be assessed at baseline before the start of the TMS Intervention (Pre-TMS, Day 0) and after the final TMS session (post-TMS, Day 5)

Study Arms (1)

Frontopolar cTBS Intervention

EXPERIMENTAL

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.

Device: Transcranial Magnetic Stimulation (TMS)

Interventions

Transcranial Magnetic Stimulation (TMS) DEVICE

Patients will receive cTBS, a five-minute protocol with inhibitory effects over the left frontal pole, using an accelerated design comprising three sessions daily for five consecutive days (15 sessions total). Stimulation will be delivered using a Magventure TMS device routinely used in clinical practice at the Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Frankfurt. TMS is generally well tolerated, with mild headache or scalp discomfort as common side effects. Localization will be based on individual MRI data: after cortical parcellation with FreeSurfer 7.4.1, the left frontal pole centroid will be extracted. Coil placement will be neuronavigated using the Localite Neuronavigator. Stimulation will be applied at 110% resting motor threshold (rMT; 3-pulse bursts at 50 Hz, 5 Hz interburst; 1800 pulses/train; 60 s intertrain). Intensity may be gradually increased until 110% rMT is reached.

Frontopolar cTBS Intervention

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Current psychotic symptoms in patients with psychotic disorders (F20, F23, F10.5)
• Contraindication against TMS or MRI
• Acute withdrawal symptoms (CIWA-Ar \> 5)

Sponsors & Collaborators

• Goethe University: lead

Study Sites (2)

Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt, Goethe-Universität

Frankfurt am Main, Hesse, 60528, Germany

RECRUITING

Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt, Goethe-Universität

Frankfurt am Main, Hesse, 60528, Germany

RECRUITING

Related Publications (4)

• Williams JB, Kobak KA. Development and reliability of a structured interview guide for the Montgomery Asberg Depression Rating Scale (SIGMA). Br J Psychiatry. 2008 Jan;192(1):52-8. doi: 10.1192/bjp.bp.106.032532.

  PMID: 18174510 BACKGROUND

• Nakovics H, Diehl A, Geiselhart H, Mann K. [Development and validation of an overall instrument to measure craving across multiple substances: the Mannheimer Craving Scale (MaCS)]. Psychiatr Prax. 2009 Mar;36(2):72-8. doi: 10.1055/s-2008-1067546. Epub 2008 Oct 15. German.

  PMID: 18924060 BACKGROUND

• Flannery BA, Volpicelli JR, Pettinati HM. Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res. 1999 Aug;23(8):1289-95.

  PMID: 10470970 BACKGROUND

• Vollstadt-Klein S, Lemenager T, Jorde A, Kiefer F, Nakovics H. Development and validation of the craving automated scale for alcohol. Alcohol Clin Exp Res. 2015 Feb;39(2):333-42. doi: 10.1111/acer.12636.

  PMID: 25684052 BACKGROUND

MeSH Terms

Conditions

Alcoholism

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Jonathan Repple, Prof. Dr.

  Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt

  PRINCIPAL INVESTIGATOR

• Mathias Luderer, Dr. med.

  Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt

  PRINCIPAL INVESTIGATOR

• Maren Schmidt-Kassow, Prof. Dr.

  Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Franka Timm, M.Sc.

CONTACT

+49 171 9225424; f.timm@med.uni-frankfurt.de

Jonathan Repple, Prof. Dr.

CONTACT

+49 17641633481; repple@em.uni-frankfurt.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: July 14, 2025
• Study Start: May 16, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

DE (2)