Neuronavigated rTMS for Treatment-Resistant Auditory Hallucinations (fuNEEG)
Functional Neuronavigated EEG and TMS-treatment of Chronic Acoustic Hallucinations
Auditory verbal hallucinations (AVH), such as hearing voices in the absence of an external sound source, are a common and distressing symptom of schizophrenia. In some patients, hallucinations persist despite treatment with antipsychotic medication. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that may reduce auditory hallucinations by decreasing activity in brain regions involved in auditory and language processing.
This randomized, double-blind, sham-controlled study will investigate whether individualized, neuronavigated inhibitory rTMS can reduce persistent auditory verbal hallucinations. Forty adults with medication-resistant auditory hallucinations will be randomly assigned to receive either active rTMS or sham stimulation.
For each participant, the stimulation target in the primary auditory cortex will be individually identified using electroencephalography (EEG), acoustic evoked potentials, and magnetic resonance imaging (MRI)-based neuronavigation. Participants will receive two rTMS sessions per day for five consecutive days. The severity of auditory hallucinations will be assessed before and after treatment and at a 28-day follow-up.
The study will also investigate whether treatment is associated with changes in brain activity and functional connectivity measured by EEG, including changes in the P300 event-related potential.
Visão geral do estudo
Status
Condições
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Tobias Welt, MD
- Número de telefone: 0041 58 389 93 40
- E-mail: tobias.welt@pukzh.ch
Estude backup de contato
- Nome: Sebastian Olbrich, Prof. Dr. med.
- Número de telefone: 0041 58 384 26 37
- E-mail: sebastian.olbrich@pukzh.ch
Locais de estudo
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Zurich, Suíça, 8032
- Recrutamento
- Psychiatric University Hospital Zurich
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Contato:
- Sebastian Olbrich, Prof. Dr. med.
- Número de telefone: 0041 58 384 26 37
- E-mail: sebastian.olbrich@pukzh.ch
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Contato:
- Tobias Welt, Dr. med.
- Número de telefone: 0041 58 384 93 40
- E-mail: tobias.welt@pukzh.ch
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Investigador principal:
- Tobias Welt, Dr. med.
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
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Written informed consent provided prior to participation
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Age 18 to 65 years
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Medication-resistant auditory hallucinations, defined as:
- At least two adequate trials of antipsychotic medication
- At least one of these trials with an atypical antipsychotic medication
- At least five episodes of auditory hallucinations per day during the preceding month
- Stable antipsychotic medication for at least 6 weeks
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Current treatment at the Psychiatric University Hospital Zurich (PUK), either in an outpatient clinic, day clinic, or inpatient ward
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Sufficient knowledge of German to understand the study procedures and assessments
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Ability to follow study procedures
Exclusion Criteria:
- Contraindications to TMS treatment, including cochlear implants, metallic devices close to the TMS coil, history of stroke, head injury, or seizures/epilepsy
- History of epileptic convulsive seizures or epileptiform potentials in previous EEG examinations
- TMS treatment within the 3 months preceding study inclusion
- Known severe hypersensitivity or severe adverse reaction to TMS
- Pregnancy or breastfeeding
- Intention to become pregnant during the study
- Major somatic comorbidities, such as renal failure, hepatic dysfunction, heart failure, or cardiovascular disease
- Current treatment with any drug that lowers the seizure threshold
- Known or suspected non-compliance, drug abuse, or alcohol abuse
- Vulnerable subjects (children, pregnant women, elderly persons)
- Inability to follow study procedures, for example due to language problems, psychological disorder, dementia, or other conditions interfering with participation
- Participation in another study involving investigational treatment within the 30 days preceding study inclusion or during the present study
- Current electroconvulsive therapy (ECT)
- Previous enrollment in the present study
- Investigator, family member of the investigator, employee, or other dependent person
- Contraindications or limitations related to the medical device as specified in the instructions for use
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Active rTMS
Participants receive individualized, neuronavigated inhibitory rTMS targeting the primary auditory cortex. The stimulation target is individually determined using EEG-based auditory evoked potentials and MRI-based neuronavigation. Treatment is administered twice daily for five consecutive days. |
Individualized neuronavigated inhibitory rTMS is applied to the primary auditory cortex. The individual stimulation target is determined using EEG-based auditory evoked potentials and MRI-based neuronavigation. Stimulation is delivered at 1 Hz on five consecutive days, with a total of 12,000 magnetic pulses administered over the treatment course. |
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Comparador Falso: Sham rTMS
Participants undergo the same treatment schedule and neuronavigation procedures as the active rTMS group using a sham coil that is visually and acoustically similar to the active coil but does not deliver active magnetic stimulation. |
Sham stimulation is administered using the same neuronavigation procedures and treatment schedule as active rTMS. A sham coil visually and acoustically resembling the active coil is used but does not deliver active magnetic stimulation. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change From Baseline in Auditory Vocal Hallucination Rating Scale (AVHRS) Score Immediately After Treatment
Prazo: Baseline to immediately after completion of the 5-day treatment period
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Change from baseline in auditory hallucination severity assessed with the Auditory Vocal Hallucination Rating Scale (AVHRS), a structured interview assessing multiple characteristics of auditory hallucinations, including frequency, duration, location, loudness, negative content, distress, interference with daily life, perceived control, anxiety, and interference with thinking. |
Baseline to immediately after completion of the 5-day treatment period
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change From Baseline in Auditory Vocal Hallucination Rating Scale (AVHRS) Score at Day 28
Prazo: Baseline to Day 28 after completion of treatment
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Change from baseline in auditory hallucination severity assessed with the Auditory Vocal Hallucination Rating Scale (AVHRS), a structured interview assessing multiple characteristics of auditory hallucinations, including frequency, duration, location, loudness, negative content, distress, interference with daily life, perceived control, anxiety, and interference with thinking. |
Baseline to Day 28 after completion of treatment
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Change From Baseline in PSYRATS Auditory Hallucinations Subscale Score Immediately After Treatment
Prazo: Baseline to immediately after completion of the 5-day treatment period
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Change from baseline in the Auditory Hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). The subscale consists of 11 items scored from 0 to 4, yielding a total score from 0 to 44. Higher scores indicate greater auditory hallucination severity. |
Baseline to immediately after completion of the 5-day treatment period
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Change From Baseline in PSYRATS Delusions Subscale Score Immediately After Treatment
Prazo: Baseline to immediately after completion of the 5-day treatment period
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Change from baseline in the Delusions subscale of the Psychotic Symptom Rating Scales (PSYRATS). The subscale consists of 6 items scored from 0 to 4, yielding a total score from 0 to 24. Higher scores indicate greater delusion severity. |
Baseline to immediately after completion of the 5-day treatment period
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Change From Baseline in PSYRATS Combined Score Immediately After Treatment
Prazo: Baseline to immediately after completion of the 5-day treatment period
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Change from baseline in the combined Psychotic Symptom Rating Scales (PSYRATS) score, calculated as the sum of the Auditory Hallucinations and Delusions subscale scores. The combined score ranges from 0 to 68, with higher scores indicating greater overall psychotic symptom severity. |
Baseline to immediately after completion of the 5-day treatment period
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Change From Baseline in PSYRATS Auditory Hallucinations Subscale Score at Day 28
Prazo: Baseline to Day 28 after completion of treatment
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Change from baseline in the Auditory Hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). The subscale consists of 11 items scored from 0 to 4, yielding a total score from 0 to 44. Higher scores indicate greater auditory hallucination severity. |
Baseline to Day 28 after completion of treatment
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Change From Baseline in PSYRATS Delusions Subscale Score at Day 28
Prazo: Baseline to Day 28 after completion of treatment
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Change from baseline in the Delusions subscale of the Psychotic Symptom Rating Scales (PSYRATS). The subscale consists of 6 items scored from 0 to 4, yielding a total score from 0 to 24. Higher scores indicate greater delusion severity. |
Baseline to Day 28 after completion of treatment
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Change From Baseline in PSYRATS Combined Score at Day 28
Prazo: Baseline to Day 28 after completion of treatment
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Change from baseline in the combined Psychotic Symptom Rating Scales (PSYRATS) score, calculated as the sum of the Auditory Hallucinations and Delusions subscale scores. The combined score ranges from 0 to 68, with higher scores indicating greater overall psychotic symptom severity. |
Baseline to Day 28 after completion of treatment
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Change From Baseline in Auditory Vocal Hallucination Rating Scale Questionnaire (AVHRS-Q) Total Score Immediately After Treatment
Prazo: Baseline to immediately after completion of the 5-day treatment period
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Change from baseline in the total score of the Auditory Vocal Hallucination Rating Scale Questionnaire (AVHRS-Q), a self-report measure assessing characteristics and severity of auditory vocal hallucinations. Higher scores indicate greater severity of auditory vocal hallucinations. |
Baseline to immediately after completion of the 5-day treatment period
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Change From Baseline in Auditory Vocal Hallucination Rating Scale Questionnaire (AVHRS-Q) Total Score at Day 28
Prazo: Baseline to Day 28 after completion of treatment
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Change from baseline in the total score of the Auditory Vocal Hallucination Rating Scale Questionnaire (AVHRS-Q), a self-report measure assessing characteristics and severity of auditory vocal hallucinations. Higher scores indicate greater severity of auditory vocal hallucinations. |
Baseline to Day 28 after completion of treatment
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Change From Baseline in Self-assessment of Auditory Verbal Hallucinations (SAVH) Total Score Immediately After Treatment
Prazo: Baseline to immediately after completion of the 5-day treatment period
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Change from baseline in the total score of the Self-assessment of Auditory Verbal Hallucinations (SAVH), a 9-item self-report measure assessing auditory verbal hallucinations during the preceding week. Each item is scored from 0 to 5, yielding a total score from 0 to 45. Higher scores indicate greater severity of auditory verbal hallucinations. |
Baseline to immediately after completion of the 5-day treatment period
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Change From Baseline in Self-assessment of Auditory Verbal Hallucinations (SAVH) Total Score at Day 28
Prazo: Baseline to Day 28 after completion of treatment
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Change from baseline in the total score of the Self-assessment of Auditory Verbal Hallucinations (SAVH), a 9-item self-report measure assessing auditory verbal hallucinations during the preceding week. Each item is scored from 0 to 5, yielding a total score from 0 to 45. Higher scores indicate greater severity of auditory verbal hallucinations. |
Baseline to Day 28 after completion of treatment
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Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score Immediately After Treatment
Prazo: Baseline to immediately after completion of the 5-day treatment period
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Change from baseline in illness severity assessed using the Clinical Global Impression-Severity (CGI-S) scale. CGI-S is rated from 1 to 7, with higher scores indicating greater illness severity. |
Baseline to immediately after completion of the 5-day treatment period
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Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Day 28
Prazo: Baseline to Day 28 after completion of treatment
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Change from baseline in illness severity assessed using the Clinical Global Impression-Severity (CGI-S) scale. CGI-S is rated from 1 to 7, with higher scores indicating greater illness severity. |
Baseline to Day 28 after completion of treatment
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Clinical Global Impression-Improvement (CGI-I) Score Immediately After Treatment
Prazo: Immediately after completion of the 5-day treatment period
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Overall change in clinical condition assessed using the Clinical Global Impression-Improvement (CGI-I) scale. CGI-I is rated from 1 to 7, where 1 indicates very much improved, 4 indicates no change, and 7 indicates very much worse. |
Immediately after completion of the 5-day treatment period
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Clinical Global Impression-Improvement (CGI-I) Score at Day 28
Prazo: Day 28 after completion of treatment
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Overall change in clinical condition assessed using the Clinical Global Impression-Improvement (CGI-I) scale. CGI-I is rated from 1 to 7, where 1 indicates very much improved, 4 indicates no change, and 7 indicates very much worse. |
Day 28 after completion of treatment
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Change From Baseline in Auditory P300 Parameters Immediately After Treatment
Prazo: Baseline to immediately after completion of the 5-day treatment period
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Change from baseline in auditory P300 event-related potential parameters measured by EEG during an auditory Oddball paradigm. P300 amplitude and latency elicited by target stimuli will be evaluated and compared between baseline and post-treatment recordings. |
Baseline to immediately after completion of the 5-day treatment period
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Change From Baseline in Auditory P300 Parameters at Day 28
Prazo: Baseline to Day 28 after completion of treatment
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Change from baseline in auditory P300 event-related potential parameters measured by EEG during an auditory Oddball paradigm. P300 amplitude and latency elicited by target stimuli will be evaluated and compared between baseline and Day-28 recordings. |
Baseline to Day 28 after completion of treatment
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Change From Baseline in EEG Functional Connectivity Immediately After Treatment
Prazo: Baseline to immediately after completion of the 5-day treatment period
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Change from baseline in functional brain connectivity assessed using EEG and source localization with low-resolution electromagnetic tomography (LORETA). Treatment-related changes in functional connectivity between cortical brain regions will be evaluated by comparing baseline and post-treatment EEG recordings. |
Baseline to immediately after completion of the 5-day treatment period
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Change From Baseline in EEG Functional Connectivity at Day 28
Prazo: Baseline to Day 28 after completion of treatment
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Change from baseline in functional brain connectivity assessed using EEG and source localization with low-resolution electromagnetic tomography (LORETA). Treatment-related changes in functional connectivity between cortical brain regions will be evaluated by comparing baseline and Day-28 EEG recordings. |
Baseline to Day 28 after completion of treatment
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Sebastian Olbrich, Prof. Dr. med., Psychiatrische Universitätsklinik Zürich
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- fuNEEG
- Bangerter-Rhyner-Foundation (Número de outro subsídio/financiamento: Gottfried & Julia Bangerter-Rhyner-Stiftung)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Individual participant data are not planned to be made publicly available. Potential reuse of pseudonymized data may be considered in accordance with participant consent and applicable ethical and data protection requirements.
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