Clinical trial NCT00783120: Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Negative Symptoms in Schizophrenia
Official title: Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Negative Symptoms in Schizophrenia - a Multicenter Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Keywords: schizophrenia, negative symptoms, TMS, magnetic stimulation
Lead sponsor: Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
Sponsor class: OTHER
Collaborators: name: University of Göttingen
First posted: 2008-10-31
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Schizophrenia is a major psychotic disorder that presents an enormous burden to the patients and their relatives. Despite treatment with second generation antipsychotics, negative symptoms and cognitive impairment often persist and determine an unfavourable course including reduction in life quality. Prefrontal repetitive transcranial magnetic stimulation (rTMS), a promising noninvasive biological technique, applied adjuvant to ongoing antipsychotic treatment was demonstrated to be safe and was associated with improvement in negative symptoms in the majority of the small placebo-controlled trials.

The primary objective of the trial is to investigate the efficacy of high-frequency rTMS (add-on to antipsychotic therapy) in the treatment of negative symptoms in schizophrenia compared to sham stimulation (placebo).


Eligibility criteria: Inclusion Criteria:

* Male or female in-patients and out-patients, 18 - 60 years of age
* Diagnostic criteria for schizophrenia according to ICD-10/DSM IV
* PANSS negative sum score \> 20 points, 1 of items N1 - N7 (range 1 to 7) ≥ 4 (at least moderate)
* Improvement in PANSS negative sum score less than 10 % in the last 2 weeks prior to study entry, stable antipsychotic medication
* Informed Consent

Exclusion Criteria:

* Clinically relevant psychiatric comorbidity, verbal IQ \< 85
* History of epileptic seizures, organic brain disease
* Instable medical comorbidity or condition
* Previous treatment by rTMS
* Factors not compatible with the use of TMS, e.g. cardiac pace makers or other metallic implants, pregnancy

Primary outcomes:
measure: Improvement in negative symptoms (baseline vs. day 21, PANNS negative sum score)
timeFrame: 105 Days
Secondary outcomes:
measure: efficacy on cognition, EPS, neuroplasticity (sMRI/MRS), depression, life quality and social function
timeFrame: 105 days
Other outcomes:
Locations:
city: Regensburg
country: Germany
facility: Department of Psychiatry and Psychotherapy, University of Regensburg
state: Bayern
city: Goettingen
country: Germany
facility: Dept. of Psychiatry and Psychotherapy, University Hospital of the Georg-August-University Göttingen
state: Niedersachsen
city: Duesseldorf
country: Germany
facility: Department of Psychiatry, Heinrich-Heine University Hospital
state: Nordrhein-Westfalen
Study officials:
affiliation: Dept. of Psychiatry and Psychotherapy, University Hospital of the Georg-August-University Göttingen
name: Peter G Falkai, Prof MD.
role: STUDY_DIRECTOR
References:
citation: Koutsouleris N, Wobrock T, Guse B, Langguth B, Landgrebe M, Eichhammer P, Frank E, Cordes J, Wolwer W, Musso F, Winterer G, Gaebel W, Hajak G, Ohmann C, Verde PE, Rietschel M, Ahmed R, Honer WG, Dwyer D, Ghaseminejad F, Dechent P, Malchow B, Kreuzer PM, Poeppl TB, Schneider-Axmann T, Falkai P, Hasan A. Predicting Response to Repetitive Transcranial Magnetic Stimulation in Patients With Schizophrenia Using Structural Magnetic Resonance Imaging: A Multisite Machine Learning Analysis. Schizophr Bull. 2018 Aug 20;44(5):1021-1034. doi: 10.1093/schbul/sbx114.
citation: Hasan A, Wobrock T, Guse B, Langguth B, Landgrebe M, Eichhammer P, Frank E, Cordes J, Wolwer W, Musso F, Winterer G, Gaebel W, Hajak G, Ohmann C, Verde PE, Rietschel M, Ahmed R, Honer WG, Dechent P, Malchow B, Castro MFU, Dwyer D, Cabral C, Kreuzer PM, Poeppl TB, Schneider-Axmann T, Falkai P, Koutsouleris N. Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia. Mol Psychiatry. 2017 Jun;22(6):857-864. doi: 10.1038/mp.2016.161. Epub 2016 Oct 11.
citation: Wobrock T, Guse B, Cordes J, Wolwer W, Winterer G, Gaebel W, Langguth B, Landgrebe M, Eichhammer P, Frank E, Hajak G, Ohmann C, Verde PE, Rietschel M, Ahmed R, Honer WG, Malchow B, Schneider-Axmann T, Falkai P, Hasan A. Left prefrontal high-frequency repetitive transcranial magnetic stimulation for the treatment of schizophrenia with predominant negative symptoms: a sham-controlled, randomized multicenter trial. Biol Psychiatry. 2015 Jun 1;77(11):979-88. doi: 10.1016/j.biopsych.2014.10.009. Epub 2014 Oct 23.
citation: Cordes J, Falkai P, Guse B, Hasan A, Schneider-Axmann T, Arends M, Winterer G, Wolwer W, Ben Sliman E, Ramacher M, Schmidt-Kraepelin C, Ohmann C, Langguth B, Landgrebe M, Eichhammer P, Frank E, Burger J, Hajak G, Rietschel M, Wobrock T. Repetitive transcranial magnetic stimulation for the treatment of negative symptoms in residual schizophrenia: rationale and design of a sham-controlled, randomized multicenter study. Eur Arch Psychiatry Clin Neurosci. 2009 Nov;259 Suppl 2:S189-97. doi: 10.1007/s00406-009-0060-y.