Neuronavigated rTMS for Treatment-Resistant Auditory Hallucinations

NCT07856368 | Recruiting

• 2 other identifiers: fuNEEGBangerter-Rhyner-Foundation
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia; Auditory Verbal Hallucinations

Keywords

Auditory Verbal Hallucinations; Treatment-Resistant Hallucinations; Repetitive Transcranial Magnetic Stimulation; rTMS; Neuronavigation; Electroencephalography; EEG; Auditory Evoked Potentials; Functional Connectivity; P300

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Auditory Vocal Hallucination Rating Scale (AVHRS) Score Immediately After Treatment

  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

Secondary Outcomes (19)

• Change From Baseline in Auditory Vocal Hallucination Rating Scale (AVHRS) Score at Day 28

  Baseline to Day 28 after completion of treatment

• Change From Baseline in PSYRATS Auditory Hallucinations Subscale Score Immediately After Treatment

  Baseline to immediately after completion of the 5-day treatment period

• Change From Baseline in PSYRATS Delusions Subscale Score Immediately After Treatment

  Baseline to immediately after completion of the 5-day treatment period

• Change From Baseline in PSYRATS Combined Score Immediately After Treatment

  Baseline to immediately after completion of the 5-day treatment period

• Change From Baseline in PSYRATS Auditory Hallucinations Subscale Score at Day 28

  Baseline to Day 28 after completion of treatment

Study Arms (2)

Active rTMS

EXPERIMENTAL

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.

Device: Neuronavigated repetitive transcranial magnetic stimulation (rTMS)

Sham rTMS

SHAM COMPARATOR

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.

Device: Sham repetitive transcranial magnetic stimulation (rTMS)

Interventions

Neuronavigated repetitive transcranial magnetic stimulation (rTMS) DEVICE

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.

Active rTMS

Sham repetitive transcranial magnetic stimulation (rTMS) DEVICE

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.

Sham rTMS

Eligibility Criteria

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

You may qualify if:

• Written informed consent provided prior to participation
• Age 18 to 65 years
• 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
• Current treatment at the Psychiatric University Hospital Zurich (PUK), either in an outpatient clinic, day clinic, or inpatient ward
• Sufficient knowledge of German to understand the study procedures and assessments
• Ability to follow study procedures

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Psychiatric University Hospital, Zurich: lead

Study Sites (1)

Psychiatric University Hospital Zurich

Zurich, 8032, Switzerland

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Hallucinations

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Sebastian Olbrich, Prof. Dr. med.

  Psychiatrische Universitätsklinik Zürich

  STUDY DIRECTOR

Central Study Contacts

Tobias Welt, MD

CONTACT

0041 58 389 93 40; tobias.welt@pukzh.ch

Sebastian Olbrich, Prof. Dr. med.

CONTACT

0041 58 384 26 37; sebastian.olbrich@pukzh.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, treatment personnel, investigators, and outcome assessors are masked to treatment allocation. Active and sham rTMS coils are indistinguishable in appearance and sound. The sham coil produces similar clicking sounds but does not deliver active magnetic stimulation. The outcome assessment team is separate from the treatment team and has no access to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomized in a 1:1 ratio to one of two parallel study arms receiving either active neuronavigated inhibitory rTMS or sham stimulation. Both groups undergo identical study procedures and assessments.

Study Record Dates

• First Submitted: September 23, 2026
• First Posted: October 2, 2026
• Study Start: June 11, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)