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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 해당 없음
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Tobias Welt, MD
- 전화번호: 0041 58 389 93 40
- 이메일: tobias.welt@pukzh.ch
연구 연락처 백업
- 이름: Sebastian Olbrich, Prof. Dr. med.
- 전화번호: 0041 58 384 26 37
- 이메일: sebastian.olbrich@pukzh.ch
연구 장소
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Zurich, 스위스, 8032
- 모병
- Psychiatric University Hospital Zurich
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연락하다:
- Sebastian Olbrich, Prof. Dr. med.
- 전화번호: 0041 58 384 26 37
- 이메일: sebastian.olbrich@pukzh.ch
-
연락하다:
- Tobias Welt, Dr. med.
- 전화번호: 0041 58 384 93 40
- 이메일: tobias.welt@pukzh.ch
-
수석 연구원:
- Tobias Welt, Dr. med.
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
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실험적: 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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가짜 비교기: 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. |
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change From Baseline in Auditory Vocal Hallucination Rating Scale (AVHRS) Score Immediately After Treatment
기간: 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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2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change From Baseline in Auditory Vocal Hallucination Rating Scale (AVHRS) Score at Day 28
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
|
공동 작업자 및 조사자
수사관
수사관
- 연구 책임자: Sebastian Olbrich, Prof. Dr. med., Psychiatrische Universitätsklinik Zürich
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- fuNEEG
- Bangerter-Rhyner-Foundation (기타 보조금/기금 번호: Gottfried & Julia Bangerter-Rhyner-Stiftung)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
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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