- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02670291
Treatment of Auditory Hallucinations in Schizophrenia With Bilateral Theta Burst Stimulation (cTBS-AH)
Study Overview
Status
Conditions
Intervention / Treatment
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hopes for new pharmacological treatment options have been disappointed and the pharmaceutical industry has apparently withdrawn from the development of new compounds for this disorder.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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Christian Plewnia, Prof. MD.
- Phone Number: +49 7071 29 86121
- Email: christian.plewnia@uni-tuebingen.de
Study Contact Backup
- Name: Bettina Brendel, PhD.
- Phone Number: + 49 7071 29 87073
- Email: bettina.brendel@uni-tuebingen.de
Study Locations
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-
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Tuebingen, Germany, 72076
- Department of Psychiatry and Psychotherapy
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- Suicidality
- History/evidence of brain surgery
- Significant brain malformation or neoplasm
- Head injury
- Cerebral vascular events
- Neurodegenerative disorder
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: active cTBS
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);
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combined active and sham coil
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Sham Comparator: Sham cTBS
Determination of resting motor threshold (RMT); Coil position: temporoparietal cortices halfway between T3/P3 and T4/P4 (EEG 10/20 system); sham cTBS;
|
combined active and sham coil
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change of Psychotic Symptom Rating Scales - Auditory Hallucinations subscale (PSYRATS-AH)
Time Frame: 3 weeks
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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.
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3 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Christian Plewnia, Prof. MD., Dept. Psychiatry and Psychotherapy, Universtiy of Tuebingen
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PL 525/4-1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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