Alcohol AddictionTMS-SUDNCT07064590
Effects of Frontopolar TMS in Alcohol Craving
A study testing Transcranial Magnetic Stimulation (TMS) in people with Alcohol Addiction, run by Goethe University at 2 sites in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcohol Addiction
- What is being tested?
- Transcranial Magnetic Stimulation (TMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 2 sitesGermany
- Study dates
- 16 May 2025to May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adults aged 18-65
- ICD-10 diagnosis of alcohol dependence
- Ability to give consent
- Sinus rhythm in ECG
Who cannot join
- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Germany2 sites, 2 recruiting
- Recruiting
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt, Goethe-Universität
Frankfurt am Main, Hesse, 60528
- Recruiting
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt, Goethe-Universität
Frankfurt am Main, Hesse, 60528
Franka Timm, +491719225424, f.timm@med.uni-frankfurt.de
Jonathan Repple, Prof. Dr., +49 17641633481, repple@em.uni-frankfurt.de
About this study
Official title: Investigation of Frontopolar Transcranial Magnetic Stimulation on Correlates of Craving in Alcohol Addiction
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:
Read more
- 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.
Read the detailed 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.
- Conditions
- Alcohol Addiction
- Being tested
- Transcranial Magnetic Stimulation (TMS)
- 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
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Transcranial Magnetic Stimulation (TMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
TMS-related changes in heart rate (HR; beats per minute) during VR-based alcohol craving induction will be assessed. HR is continuously recorded throughout each VR cue exposure session. For each session, the difference in minimum and maximum HR (within-session change) will be calculated as an index of physiological craving reactivity. These within-session changes are then compared between sessions (Day 1 → Day 5) to evaluate TMS-induced modulation of HR responses. Further indices that can be derived from this assessment are mean, maximum, and minimum HR.
Measured: 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
TMS-related changes in skin conductance (SC; µS) will be assessed during VR-based alcohol craving induction. SC is continuously recorded throughout each VR cue exposure session. For each session, the difference in minimum and maximum SC (within-session change) will be calculated as an index of physiological craving reactivity. These within-session changes are then compared between sessions (Day 1 → Day 5) to evaluate TMS-induced modulation of SC responses. Further indices that can be derived from this assessment are mean, maximum, and minimum SC.
Measured: 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
TMS-related changes in skin temperature (ST; °C) are assessed during VR-based alcohol craving induction. ST is continuously recorded throughout each VR cue exposure session. For each session, the difference in minimum and maximum ST (within-session change) will be calculated as an index of physiological craving reactivity. These within-session changes are then compared between sessions (Day 1 → Day 5) to evaluate TMS-induced modulation of ST responses. Further indices that can be derived from this assessment are mean, maximum, and minimum ST.
Measured: 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)
TMS-related changes in subjective craving ratings will be measured before and after each VR alcohol cue exposure. Participant reactivity during VR alcohol cue exposure is assessed using a 10-item Visual Analog Scale (VAS; 0-100). Items measure both general affective/physiological states (e.g., tension, stress, feeling challenged, control) and alcohol-related urges (e.g., thoughts, desire, craving for alcohol). Each item is rated from 0 ("not at all") to 100 ("very"/"strong"). The mean score across all 10 items will be calculated. Additionally, individual item scores will be calculated separately to investigate item-specific/domain-specific changes. VAS ratings are obtained immediately before and immediately after each VR session to assess changes in reactivity following alcohol cue exposure. Additionally, VAS rating assessed before the TMS intervention and after the final TMS session will be compared to assess TMS-related changes in craving reactivity.
Measured: 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)
Changes in self-reported psychological alcohol craving will be assessed using the Mannheimer Craving Scale (MaCS) before and after the frontopolar TMS intervention. The MaCS measures obsessive-compulsive symptoms related to substance use and dependence. It includes 12 core items and 4 additional items. Each of the 12 core items is rated on a 5-point Likert scale (0-4), with higher values indicating greater symptom intensity. The four additional items include three visual analog scales (VAS; 0-100) assessing average craving intensity, maximum craving intensity, and craving frequency during the past seven days, as well as one item assessing duration of abstinence (in days). The mean total score of the 12 core items (range: 0-4) will be computed. VAS measures and abstinence duration will be analyzed separately as supplementary indicators of craving. Exploratory analysis could also include the calculation of mean scores of subscales.
Measured: 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)
TMS-induced change in self-reported psychological craving assessed by the Craving-Automatized-Scale-Alcohol (CAS-A)
The CAS-A is a 15-item self-report questionnaire that assesses situations of loss of control or automatic drinking, and is here implemented to evaluate changes in self-reported psychological craving before and after TMS intervention. Each item is rated on a 6-point Likert scale (0 = "never" to 5 = "always"), referring to the participant's most recent drinking episode within the last 7 days. Item 16 records when the participant last consumed alcohol. The mean total score across all 15 items will be calculated. Additionally, further mean subscale scores (e.g., 5 CAS-A factors as "only aware in hindsight," "no deliberate decision," "contrary to intention," "no perception," and "no control"; or 2 factors, "unaware" and "nonvolitional.") will be used to explore distinct dimensions of craving and drinking behavior.
Measured: The CAS-A 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)
Correlation between baseline brain connectivity and changes in heart rate (BPM) increase during VR
Correlation between baseline structural or functional brain connectivity (as assessed via MRI prior to TMS) and the increase in heart rate during VR craving induction. Connectivity data are derived using diffusion-weighted imaging and resting-state fMRI, processed via CATO and analyzed using network-based statistics.
Measured: MRI and, therefore, structural and functional connectivity is assessed at baseline (Day 0) and heart rate change during VR sessions before TMS intervention (Day 1) and after the final TMS intervention (Day 5)
TMS-induced changes in clinician-reported depressive symptoms using the MADRS
Changes in self-reported craving levels will be measured before and after the 5-day TMS intervention, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), is a 10-item, clinician-administered scale to assess depression severity. It rates symptoms like sadness, feelings of emptiness, tension, and reduced interest, with scores from 0 to 6 for each item, resulting in a total score from 0 to 60. Higher scores indicate more severe depressive symptoms.
Measured: The MADRS 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2025
- Study start16 May 2025
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Alcohol AddictionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Goethe University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jonathan Repple, Goethe University
- Investigators
- Jonathan Repple, Prof. Dr., Principal investigator, Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum FrankfurtMathias Luderer, Dr. med., Principal investigator, Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum FrankfurtMaren Schmidt-Kassow, Prof. Dr., Principal investigator, Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07064590
- Sponsor's protocol ID
- 2024-2021
- Acronym
- TMS-SUD
- Status last verified
- Jan 2026
- First submitted
- 6 Jun 2025
- Last updated
- 22 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 18174510Nakovics 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.
PubMed 18924060Flannery BA, Volpicelli JR, Pettinati HM. Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res. 1999 Aug;23(8):1289-95.
PubMed 10470970Vollstadt-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.
PubMed 25684052
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Frontopolar Transcranial Magnetic Stimulation on Correlates of Craving in Alcohol Addiction
- ClinicalTrials.gov ID
- NCT07064590
- Acronym / sponsor ID
- TMS-SUD / 2024-2021
- 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
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Goethe UniversityUniversity, hospital or other
- Study start
- 16 May 2025 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 14 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Frontopolar cTBS Intervention | Experimental | Device: Transcranial Magnetic Stimulation (TMS)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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- adults aged 18-65
- ICD-10 diagnosis of alcohol dependence
- Ability to give consent
- Sinus rhythm in ECG
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic Stimulation (TMS)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. | Device | Frontopolar cTBS Intervention |
Primary outcome
TMS-induced changes in psychological alcohol craving assessed with the Penn Alcohol Craving Scale (PACS)
Time frame: 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)
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).
8 secondary outcomes
TMS-induced change in heart rate (BPM) during virtual reality alcohol cue exposure
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
TMS-induced change in self-reported psychological craving assessed by the Craving-Automatized-Scale-Alcohol (CAS-A)
Time frame: The CAS-A 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)
Correlation between baseline brain connectivity and changes in heart rate (BPM) increase during VR
Time frame: MRI and, therefore, structural and functional connectivity is assessed at baseline (Day 0) and heart rate change during VR sessions before TMS intervention (Day 1) and after the final TMS intervention (Day 5)
TMS-induced changes in clinician-reported depressive symptoms using the MADRS
Time frame: The MADRS 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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2026.
- Background: PubMed 18174510Williams 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.
- Background: PubMed 18924060Nakovics 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.
- Background: PubMed 10470970Flannery BA, Volpicelli JR, Pettinati HM. Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res. 1999 Aug;23(8):1289-95.
- Background: PubMed 25684052Vollstadt-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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jonathan Repple, Prof. Dr. principal investigator
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt
Mathias Luderer, Dr. med. principal investigator
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt
Maren Schmidt-Kassow, Prof. Dr. principal investigator
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation (TMS) in people with Alcohol Addiction, run by Goethe University at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Franka Timm, M.Sc. (+49 171 9225424, f.timm@med.uni-frankfurt.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TMS-induced changes in psychological alcohol craving assessed with the Penn Alcohol Craving Scale (PACS) (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07064590, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2026.