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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

Tracking Information
First Submitted Date  ICMJE January 26, 2016
First Posted Date  ICMJE February 1, 2016
Last Update Posted Date April 19, 2019
Actual Study Start Date  ICMJE January 2017
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 1, 2016)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 29, 2016)
Change of PSYRATS-AH [ Time Frame: 3 weeks ]
Group comparison (active vs. sham cTBS) regarding the change of the PSYRATS-AH score from baseline to end of treatment period.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment of Auditory Hallucinations in Schizophrenia With Bilateral Theta Burst Stimulation
Official Title  ICMJE Treatment of Auditory Hallucinations in Schizophrenia With Bilateral Theta Burst Stimulation
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Auditory Hallucinations
  • Schizophrenia
Intervention  ICMJE Device: MagPro Cool-B65A/P, Magventure
combined active and sham coil
Study Arms  ICMJE
  • 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);
    Intervention: Device: MagPro Cool-B65A/P, Magventure
  • 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;
    Intervention: Device: MagPro Cool-B65A/P, Magventure
Publications * Plewnia 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 11, 2016)
86
Original Estimated Enrollment  ICMJE
 (submitted: January 29, 2016)
64
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02670291
Other Study ID Numbers  ICMJE PL 525/4-1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital Tuebingen
Study Sponsor  ICMJE University Hospital Tuebingen
Collaborators  ICMJE
  • German Research Foundation
  • Universität Tübingen
Investigators  ICMJE
Principal Investigator: Christian Plewnia, Prof. MD. Dept. Psychiatry and Psychotherapy, Universtiy of Tuebingen
PRS Account University Hospital Tuebingen
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP