Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02670291 |
| Other study ID # |
PL 525/4-1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 2017 |
| Est. completion date |
March 2024 |
Study information
| Verified date |
June 2022 |
| Source |
University Hospital Tuebingen |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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. 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.
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.
