Auditory HallucinationscTBS-AHNCT02670291
Treatment of Auditory Hallucinations in Schizophrenia With Bilateral Theta Burst Stimulation
A study testing MagPro Cool-B65A/P, Magventure in people with Auditory Hallucinations and Schizophrenia, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
This randomized, sham-controlled, double blind, multicentre clinical trial aims at providing evidence for the efficacy and safety of continuous theta burst stimulation (cTBS) in the treatment of auditory hallucinations in patients with schizophrenia. Overall, the study will include 137 patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Auditory Hallucinations, Schizophrenia
- What is being tested?
- MagPro Cool-B65A/P, Magventure
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 138 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2017to Mar 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Men and women, age 18-65 years
- Schizophrenia (DSM-5 295.90), schizophreniform disorder (DSM-5, 295.40), or schizoaffective disorder (DSM-5 295.70)
- Auditory hallucinations (AH) present at least once a week, for at least 3 months
- No sufficient effect of at least one adequate antipsychotic treatment
- Severity according to PANSS hallucination score (Item P3) of 3 or more
- Fluent German language
- Stable antipsychotic medication 2 weeks before and 3 weeks during the treatment
Who cannot join
- Suicidality
- History/evidence of brain surgery
- Significant brain malformation or neoplasm
- Head injury
- Cerebral vascular events
- Neurodegenerative disorder
Show all 13Show fewer
- Deep brain stimulation
- Intracranial metallic particles
- History of seizures
- Diagnose of substance dependence or abuse as primary clinical problem
- Severe somatic comorbidity
- Cardiac pacemakers
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
This randomized, sham-controlled, double blind, multicentre clinical trial aims at providing evidence for the efficacy and safety of continuous theta burst stimulation (cTBS) in the treatment of auditory hallucinations in patients with schizophrenia. Overall, the study will include 137 patients. Because of the adaptive study design, an interim analysis was performed after half of the originally planned patients (43/86), according to which the sample size was increased by 51 patients). Each patient will receive a three weeks course of daily (5/week) treatment; 50% of the patients will be treated with cTBS (1200 impulses daily), the other half with a sham stimulation to the left and right temporoparietal cortex. Sham stimulation will be applied by an active sham-coil that allows for a double-blind treatment. Follow-up assessments 1, 3 and 6 months after treatment will investigate the stability of treatment effects.
Read the detailed description
Auditory verbal hallucinations (AH), a cardinal feature of schizophrenia, are often severely distressing and increase the risk for violence and suicide. Although antipsychotic medication mostly exerts rapid beneficial effects on this symptom particularly in first-episode patients who continue on taking their medication (Sommer et al. 2012), in up to 25%-30% of all patients, such hallucinations persist (Shergill et al. 1998). The often progressive course of the disease and insufficient treatment adherence due to unwanted side effects significantly limit the treatment response. In turn, this lack of treatment efficacy also contributes to low treatment adherence which is generally associated with an unfavorable course of schizophrenia and increased relapse and readmission rate. New and effective treatments are therefore essential to reduce the massive individual burden and psychosocial costs associated with schizophrenia. Nevertheless, in the last decades, the hopes for new pharmacological treatment options have been disappointed and the pharmaceutical industry has apparently withdrawn from the development of new compounds for this disorder. Accordingly, the development of non-pharmacological approaches based on an increasing body of patho-physiological knowledge is even more needed to pave new ways for the treatment of this frequently detrimental symptom of schizophrenia.
The main objective of the present study is to provide high-level evidence for efficacy and safety of continuous theta burst stimulation (cTBS) in the treatment of auditory hallucination (AH) by this first full-size multicenter (3 centers) controlled clinical trial.
This is a double blind (actually triple blind, i.e. patient, clinical investigator, and person who will administer cTBS), randomized, sham-controlled clinical trial to test the efficacy and safety of bilateral (successively applied) daily cTBS to the temporoparietal cortex on the severity of AH. The study will be conducted in a two-armed parallel design in which 50 % of the patients will be treated with the verum stimulation and the other half of patients will receive the placebo / sham stimulation.
The cTBS protocol follows the method by Huang et al. (2005) and our pilot study (Plewnia et al. 2014a) to achieve a lasting reduction of cortical excitability. Accordingly, each stimulation train (40 s) of cTBS consists of 600 stimuli applied in bursts of 3 pulses at 50 Hz given every 200 ms (5 Hz). Stimulation intensity is standardized at 80% of the resting motor threshold (RMT) and applied successively to each hemisphere. For the first session, the order of right and left hemisphere will be determined by randomization and will alternate in each following session to preclude order effects.The RMT will be determined using EMG recordings from the left and right abductor pollicis brevis and defined as the minimal stimulation intensity needed to elicit at least 10 out of 20 motor-evoked-potentials of ≥ 50µV. RMT will be determined once, i.e. before the beginning of treatment period. The cTBS or sham treatment will be targeted both temporoparietal cortices halfway between T3/P3 and T4/P4 (EEG 10/20 system).
The treatment (active cTBS or sham cTBS) will be administered over a period of 3 consecutive weeks at each workday (Monday to Friday), resulting in a total of 15 treatment sessions. Ratings will be performed after the last treatment of each week by an independent rater. Follow-up visits are planned 1, 3 and 6 months after end of treatment phase to control for sustainability of cTBS treatment effects.
- Conditions
- Auditory Hallucinations, Schizophrenia
- Being tested
- MagPro Cool-B65A/P, Magventure
- Keywords
- auditory hallucinations, schizophrenia, cTBS, noninvasive brain stimulation
- Medical subject headings
- Hallucinations, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MagPro Cool-B65A/P, MagventureDevice
combined active and sham coil
MagPro Cool-B65A/P, MagventureDevice
combined active and sham coil
| Study group | Role | What they receive |
|---|---|---|
| active cTBS | Active comparator | Determination of resting motor threshold (RMT); Coil position: temporoparietal cortices halfway between T3/P3 and T4/P4 (EEG 10/20 system); active cTBS (80% of RMT); Receives: Device: MagPro Cool-B65A/P, Magventure |
| Sham cTBS | Sham comparator | Determination of resting motor threshold (RMT); Coil position: temporoparietal cortices halfway between T3/P3 and T4/P4 (EEG 10/20 system); sham cTBS; Receives: Device: MagPro Cool-B65A/P, Magventure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of Psychotic Symptom Rating Scales - Auditory Hallucinations subscale (PSYRATS-AH)
Group comparison (active vs. sham cTBS) regarding the change of the auditory hallucination subscale of the Psychotic Symptom Rating Scales (PSYRATS-AH) score from baseline to end of treatment period.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2016 (estimated)
- Study startJan 2017
- Primary completionNov 2023
- Study completionMar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Auditory HallucinationsStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 138 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- German Research Foundation, Institute for Clinical Epidemiology and Applied Biometry, University Tuebingen, Germany, Center for Clinical Studies, University Tuebingen (ZKS), Germany, Ludwig-Maximilians - University of Munich, University of Ulm, Heidelberg University, Department of Psychiatry and Psychotherapy; Unversity Augsburg, Germany, Department of Psychiatry and Psychotherapy, LVR Duesseldorf, Germany
- Responsible party
- Sponsor
- Investigators
- Christian Plewnia, Prof. MD., Principal investigator, Dept. Psychiatry and Psychotherapy, Universtiy of Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02670291
- Sponsor's protocol ID
- PL 525/4-1
- Acronym
- cTBS-AH
- Status last verified
- Jun 2022
- First submitted
- 26 Jan 2016
- Last updated
- 25 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Plewnia C, Brendel B, Schwippel T, Becker-Sadzio J, Hajiyev I, Pross B, Strube W, Hasan A, Campana M, Padberg F, Mayer P, Kujovic M, Lorenz S, Schonfeldt-Lecuona C, Otte ML, Wolf RC, Hoppner-Buchmann J, Serna-Higuita LM, Martus P, Fallgatter AJ. Theta burst stimulation of temporo-parietal cortex regions for the treatment of persistent auditory hallucinations: a multicentre, randomised, sham-controlled, triple-blind phase 3 trial in Germany. Lancet Psychiatry. 2025 Sep;12(9):638-649. doi: 10.1016/S2215-0366(25)00202-0. Epub 2025 Aug 4.
PubMed 40774272Plewnia C, Brendel B, Schwippel T, Martus P, Cordes J, Hasan A, Fallgatter AJ. Treatment of auditory hallucinations with bilateral theta burst stimulation (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter trial. Eur Arch Psychiatry Clin Neurosci. 2018 Oct;268(7):663-673. doi: 10.1007/s00406-017-0861-3. Epub 2017 Dec 9.
PubMed 29224040
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Auditory Hallucinations in Schizophrenia With Bilateral Theta Burst Stimulation
- ClinicalTrials.gov ID
- NCT02670291
- Acronym / sponsor ID
- cTBS-AH / PL 525/4-1
- Conditions
- Auditory Hallucinations, Schizophrenia
- Keywords
- auditory hallucinations, schizophrenia, cTBS, noninvasive brain stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 138 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Collaborators
- German Research Foundation, Institute for Clinical Epidemiology and Applied Biometry, University Tuebingen, Germany, Center for Clinical Studies, University Tuebingen (ZKS), Germany, Ludwig-Maximilians - University of Munich, University of Ulm, Heidelberg University, Department of Psychiatry and Psychotherapy; Unversity Augsburg, Germany, Department of Psychiatry and Psychotherapy, LVR Duesseldorf, Germany
- Study start
- Jan 2017 (actual)
- Primary completion
- Nov 2023 (actual)
- Study completion
- Mar 2024 (actual)
- First posted
- 1 Feb 2016 (estimated)
- 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.
This randomized, sham-controlled, double blind, multicentre clinical trial aims at providing evidence for the efficacy and safety of continuous theta burst stimulation (cTBS) in the treatment of auditory hallucinations in patients with schizophrenia. Overall, the study will include 137 patients. Because of the adaptive study design, an interim analysis was performed after half of the originally planned patients (43/86), according to which the sample size was increased by 51 patients). Each patient will receive a three weeks course of daily (5/week) treatment; 50% of the patients will be treated with cTBS (1200 impulses daily), the other half with a sham stimulation to the left and right temporoparietal cortex. Sham stimulation will be applied by an active sham-coil that allows for a double-blind treatment. Follow-up assessments 1, 3 and 6 months after treatment will investigate the stability of treatment effects.
Detailed description
Auditory verbal hallucinations (AH), a cardinal feature of schizophrenia, are often severely distressing and increase the risk for violence and suicide. Although antipsychotic medication mostly exerts rapid beneficial effects on this symptom particularly in first-episode patients who continue on taking their medication (Sommer et al. 2012), in up to 25%-30% of all patients, such hallucinations persist (Shergill et al. 1998). The often progressive course of the disease and insufficient treatment adherence due to unwanted side effects significantly limit the treatment response. In turn, this lack of treatment efficacy also contributes to low treatment adherence which is generally associated with an unfavorable course of schizophrenia and increased relapse and readmission rate. New and effective treatments are therefore essential to reduce the massive individual burden and psychosocial costs associated with schizophrenia. Nevertheless, in the last decades, the hopes for new pharmacological treatment options have been disappointed and the pharmaceutical industry has apparently withdrawn from the development of new compounds for this disorder. Accordingly, the development of non-pharmacological approaches based on an increasing body of patho-physiological knowledge is even more needed to pave new ways for the treatment of this frequently detrimental symptom of schizophrenia.
The main objective of the present study is to provide high-level evidence for efficacy and safety of continuous theta burst stimulation (cTBS) in the treatment of auditory hallucination (AH) by this first full-size multicenter (3 centers) controlled clinical trial.
This is a double blind (actually triple blind, i.e. patient, clinical investigator, and person who will administer cTBS), randomized, sham-controlled clinical trial to test the efficacy and safety of bilateral (successively applied) daily cTBS to the temporoparietal cortex on the severity of AH. The study will be conducted in a two-armed parallel design in which 50 % of the patients will be treated with the verum stimulation and the other half of patients will receive the placebo / sham stimulation.
The cTBS protocol follows the method by Huang et al. (2005) and our pilot study (Plewnia et al. 2014a) to achieve a lasting reduction of cortical excitability. Accordingly, each stimulation train (40 s) of cTBS consists of 600 stimuli applied in bursts of 3 pulses at 50 Hz given every 200 ms (5 Hz). Stimulation intensity is standardized at 80% of the resting motor threshold (RMT) and applied successively to each hemisphere. For the first session, the order of right and left hemisphere will be determined by randomization and will alternate in each following session to preclude order effects.The RMT will be determined using EMG recordings from the left and right abductor pollicis brevis and defined as the minimal stimulation intensity needed to elicit at least 10 out of 20 motor-evoked-potentials of ≥ 50µV. RMT will be determined once, i.e. before the beginning of treatment period. The cTBS or sham treatment will be targeted both temporoparietal cortices halfway between T3/P3 and T4/P4 (EEG 10/20 system).
The treatment (active cTBS or sham cTBS) will be administered over a period of 3 consecutive weeks at each workday (Monday to Friday), resulting in a total of 15 treatment sessions. Ratings will be performed after the last treatment of each week by an independent rater. Follow-up visits are planned 1, 3 and 6 months after end of treatment phase to control for sustainability of cTBS treatment effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| active cTBS | Active comparator | Device: MagPro Cool-B65A/P, MagventureDetermination of resting motor threshold (RMT); Coil position: temporoparietal cortices halfway between T3/P3 and T4/P4 (EEG 10/20 system); active cTBS (80% of RMT); |
| Sham cTBS | Sham comparator | Device: MagPro Cool-B65A/P, MagventureDetermination of resting motor threshold (RMT); Coil position: temporoparietal cortices halfway between T3/P3 and T4/P4 (EEG 10/20 system); sham cTBS; |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Men and women, age 18-65 years
- Schizophrenia (DSM-5 295.90), schizophreniform disorder (DSM-5, 295.40), or schizoaffective disorder (DSM-5 295.70)
- Auditory hallucinations (AH) present at least once a week, for at least 3 months
- No sufficient effect of at least one adequate antipsychotic treatment
- Severity according to PANSS hallucination score (Item P3) of 3 or more
Key exclusion criteria (13 listed)
- Suicidality
- History/evidence of brain surgery
- Significant brain malformation or neoplasm
- Head injury
- Cerebral vascular events
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 |
|---|---|---|
| MagPro Cool-B65A/P, Magventurecombined active and sham coil | Device | active cTBS |
| MagPro Cool-B65A/P, Magventurecombined active and sham coil | Device | Sham cTBS |
Primary outcome
Change of Psychotic Symptom Rating Scales - Auditory Hallucinations subscale (PSYRATS-AH)
Time frame: 3 weeks
Group comparison (active vs. sham cTBS) regarding the change of the auditory hallucination subscale of the Psychotic Symptom Rating Scales (PSYRATS-AH) score from baseline to end of treatment period.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2024.
- Derived from this study: PubMed 40774272Plewnia C, Brendel B, Schwippel T, Becker-Sadzio J, Hajiyev I, Pross B, Strube W, Hasan A, Campana M, Padberg F, Mayer P, Kujovic M, Lorenz S, Schonfeldt-Lecuona C, Otte ML, Wolf RC, Hoppner-Buchmann J, Serna-Higuita LM, Martus P, Fallgatter AJ. Theta burst stimulation of temporo-parietal cortex regions for the treatment of persistent auditory hallucinations: a multicentre, randomised, sham-controlled, triple-blind phase 3 trial in Germany. Lancet Psychiatry. 2025 Sep;12(9):638-649. doi: 10.1016/S2215-0366(25)00202-0. Epub 2025 Aug 4.
- Derived from this study: PubMed 29224040Plewnia C, Brendel B, Schwippel T, Martus P, Cordes J, Hasan A, Fallgatter AJ. Treatment of auditory hallucinations with bilateral theta burst stimulation (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter trial. Eur Arch Psychiatry Clin Neurosci. 2018 Oct;268(7):663-673. doi: 10.1007/s00406-017-0861-3. Epub 2017 Dec 9.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Christian Plewnia, Prof. MD. principal investigator
Dept. Psychiatry and Psychotherapy, Universtiy of Tuebingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MagPro Cool-B65A/P, Magventure in people with Auditory Hallucinations and Schizophrenia, run by University Hospital Tuebingen at 1 site 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 7 inclusion and 13 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: finished, as of the sponsor's last update on 25 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Psychotic Symptom Rating Scales - Auditory Hallucinations subscale (PSYRATS-AH) (time frame: 3 weeks). 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 NCT02670291, which also lists 2 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 25 Mar 2024.