ISRCTN - ISRCTN61109178: Transcranial Magnetic Stimulation (TMS) treatment study in auditory verbal hallucinations

Plain English Summary

Background and study aims
Auditory hallucinations are a common and often stressful symptom of psychiatric patients. About a third of patients do not respond to common drug treatments. In these patients, repetitive transcranial magnetic stimulation (rTMS) has been demonstrated as an effective therapy. The aims of this study are to improve the currently existing TMS treatment by evaluating the effects of the new theta burst protocol. The duration of effects is an important issue when establishing a new therapy. The theta burst protocol has shown longer lasting after effects as compared to previously used TMS protocols. We also aim to investigate the effects of TMS on cerebral blood flow. So far, it is not entirely clear why and how TMS works. We want to investigate the neuronal activity in language-related brain areas before and after TMS treatment with magnetic resonance imaging techniques.

Who can participate?
Patients with schizophrenia or schizoaffective disorder, suffering from medication-resistant auditory verbal hallucinations.

What does the study involve?
Participants will be randomly allocated to undergo a two-week treatment with TMS or a control treatment. Two magnetic resonance sessions and several psychopathology assessments have to be conducted.

What are the possible benefits and risks of participating?
Several studies of transcranial magnetic stimulation therapy for auditory hallucinations have shown significant positive effects. The patients included in the study suffer from medication resistant auditory hallucinations, a symptom that is often stressful and reduces quality of life. One possible benefit is a reduction of auditory hallucinations in the active treatment groups. 20-25% of patients have minor headaches at the beginning of the treatment period. In rare cases epileptic seizures have been reported. To minimize the risk of seizures several electroencephalography measurements will be conducted before and throughout the study. The study will be interrupted if we detect signs of elevated risk of seizures.

Where is the study run from?
The study takes place in the University Hospital of Psychiatry (Switzerland).

When is study starting and how long is it expected to run for?
Patients will be enrolled in the study from December 2008 to December 2012.

Who is funding the study?
Swiss National Fund (Switzerland).

Who is the main contact?
Dr Jochen Kindler, PD Dr Daniela Hubl and Prof. Dr Thomas Dierks
Tel: +41 31 930 9111

Study website

Contact information

Type

Scientific

Contact name

Dr Jochen Kindler

ORCID ID

Contact details

University Hospital of Psychiatry
University of Bern
Bolligenstrasse 111
Bern
3000
Switzerland
+41 31 930 9111
jochen.kindler@puk.unibe.ch

Additional identifiers

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Transcranial Magnetic Stimulation (TMS) treatment study in auditory verbal hallucinations: a randomised controlled trial

Acronym

Study hypothesis

1. Theta-burst TMS is superior to previously used repetitive transcranial magnetic stimulation (rTMS) protocols concerning onset, extent and duration of reduction of auditory verbal hallucinations.
2. TMS effects are due to a reduction of neuronal activity in language related regions as measured by arterial spin labeling.

Ethics approval(s)

Bern Cantonal Ethics Committee (Kantonale Ethikkommission Bern), 08/12/2008, ref:EK 112/08

Study design

Randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Schizophrenia or schizoaffective disorder, medication resistant auditory hallucinations

Intervention

1. Theta Burst transcranial magnetic stimulation (TBS group)
2. 1Hz transcranial magnetic stimulation and
3. Control group (treatment as usual)

A custom TMS stimulator (MagPro R 100, Medtronic Functional Diagnostics, Skovlunde, Denmark) is used to generate repetitive biphasic magnetic pulses. Magnetic pulses are delivered with a figure-8-coil (Magnetic Coil Transducer MC-B70, Medtronic). During the experiment, rTMS pulse intensity is adjusted to 90% of the motor threshold. Patients will be randomly assigned to receive a 1 Hz or theta burst (TBS) TMS protocol. In both treatment groups, the target area is stimulated for 10 consecutive days. Stimulation at 1 Hz was applied once a day, 4min on day 1, 8min on day 2 and 16min from day 3-10.

In the TBS group, each burst contains 3 pulses at 30 Hz, repeated with an interburst interval of 100 ms. TBS is applied in double trains with a 15 min intertrain interval. On the first 3 days, 2 double trains of TBS will be applied, whereas on days 310, 1 double TBS train was applied. Safety protocols are in accordance with international safety standards of rTMS experimentation.

The control group is receiving treatment as usual.

Magnetic resonance imaging and psychopathological ratings are performed one day before the start and on the last day of the study

Intervention type

Other

Primary outcome measure

1. Psychopathology rates:
1.1. Positive and negative symtpom scale
1.2. Psychotic Symptom Rating Scales (PSYRATS)
1.3. Auditory hallucination rating scale
2. Cerebral blood flow as measured by magnetic resonance arterial spin labeling

Secondary outcome measures

1. Comparison of conventionally used 10-20 EEG coil placement approach with a frameless steretactic neuronavigation system to functionally defined (fMRI) target area
2. TMS effects on electroencephalography measures
3. Assessment of side effects

Overall study start date

15/12/2008

Overall study end date

31/12/2012

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Diagnosis of schizophrenia or schizoaffective disorder according to ICD-10
2. Medication-resistant auditory verbal hallucinations
3. 1865-years of age, and right-handed
4. Therapy refractoriness is defined as non response to at least 2 antipsychotic treatments in common dosages, each administered for at least 8 weeks

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

30-45

Participant exclusion criteria

1. History of epileptic seizures
2. Signs of elevated neuronal activity by electroencephalography (EEG)
3. Magnetic resonance (MR) contraindications, and
4. Medical disorders other than schizophrenia or schizoaffective disorder

Recruitment start date

15/12/2008

Recruitment end date

31/12/2012

Locations

Countries of recruitment

Switzerland

Study participating centre

University Hospital of Psychiatry
Bern
3000
Switzerland

Sponsor information

Organisation

Swiss National Fund (Switzerland)

Sponsor type

Government

Website

http://www.snf.ch

ROR

https://ror.org/00yjd3n13

Funders

Funder type