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Treatment of Auditory Hallucinations in Schizophrenia With Bilateral Theta Burst Stimulation (cTBS-AH)

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ClinicalTrials.gov Identifier: NCT02670291
Recruitment Status : Recruiting
First Posted : February 1, 2016
Last Update Posted : April 19, 2019
Sponsor:
Collaborators:
German Research Foundation
Universität Tübingen
Information provided by (Responsible Party):
University Hospital Tuebingen

Brief 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 86 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.

Condition or disease Intervention/treatment Phase
Auditory Hallucinations Schizophrenia Device: MagPro Cool-B65A/P, Magventure Not Applicable

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 % (n = 43) of the patients will be treated with the verum stimulation and the other half (n = 43) 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 in alternating order, counterbalanced across sessions and patients. 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 re-evaluated and adapted at the beginning of each week of treatment. The cTBS or sham treatment will be targeted to 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Auditory Hallucinations in Schizophrenia With Bilateral Theta Burst Stimulation
Actual Study Start Date : January 2017
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

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);
Device: MagPro Cool-B65A/P, Magventure
combined active and sham coil

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;
Device: MagPro Cool-B65A/P, Magventure
combined active and sham coil




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women, age 18-60 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02670291


Contacts
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Contact: Christian Plewnia, Prof. MD. +49 7071 29 86121 christian.plewnia@uni-tuebingen.de
Contact: Bettina Brendel, PhD. + 49 7071 29 87073 bettina.brendel@uni-tuebingen.de

Locations
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Germany
Department of Psychiatry and Psychotherapy Recruiting
Tuebingen, Germany, 72076
Contact: Christian Plewnia, Prof. MD.    +49 7071 29 86121    christian.plewnia@uni-tuebingen.de   
Sponsors and Collaborators
University Hospital Tuebingen
German Research Foundation
Universität Tübingen
Investigators
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Principal Investigator: Christian Plewnia, Prof. MD. Dept. Psychiatry and Psychotherapy, Universtiy of Tuebingen
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT02670291    
Other Study ID Numbers: PL 525/4-1
First Posted: February 1, 2016    Key Record Dates
Last Update Posted: April 19, 2019
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University Hospital Tuebingen:
auditory hallucinations
schizophrenia
cTBS
noninvasive brain stimulation
Additional relevant MeSH terms:
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Hallucinations
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases