|- candidate number||3048|
|- NTR Number||NTR1261|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||1-mrt-2008|
|- Secondary IDs||2008/058 METC|
|- Public Title||Effect of high frequency rTMS on negative symptoms and cognitive functioning in schizophrenia |
|- Scientific Title||Effect of high frequency transcranial magnetic stimulation on negative symptoms and cognitive functioning in schizophrenia: a combined treatment and neuroimaging study|
|- ACRONYM||TreNSS |
|- hypothesis||Brain activity in people with schizophrenia differs when compared to brain activity of people who do not have this condition. There is evidence that the negative symptoms of schizophrenia are related to reduced cortical activation involving the prefrontal cortex, in particular the activation in the dorsolateral prefrontal cortex (DLPFC) seems to be reduced. The reduced activity in the frontal cortex correlates with the severity of negative symptoms. Furthermore, several publications on functional neuroimaging literature suggest that hypofrontality in schizophrenia may be related to both negative symptoms and cognitive deficits. Transcranial magnetic stimulation (TMS) is a non-invasive, save method to stimulate the cerebral cortex and thereby alter neuronal function. In TMS a coil, which delivers brief magnetic pulses is placed adjacent to the scalp. The magnetic field passes the skull without hindrance and induces an electric current in certain brain regions. The neuronal pathways may be excited or inhibited, depending on the intensity and frequency of stimulation. Low frequency TMS (1 Hz) decreases brain activity and high frequency TMS (>5 Hz) increases brain activity.
As mentioned earlier, the brain activity in the DLPFC is reduced in people suffering from schizophrenia. Increasing brain activity in the DLPFC by using bilateral high frequency rTMS might therefore prove an effective treatment of negative symptoms and cognitive functioning in schizophrenia.|
|- Healt Condition(s) or Problem(s) studied||Schizophrenia, Negative symptoms, Transcranial magnetic stimulation (TMS), Transcranial magnetic stimulation (TMS), Cognitive functioning|
|- Inclusion criteria||1. Participants must be 18 years or older. |
2. They must be diagnosed with schizophrenia and the diagnosis must be confirmed by a standardised psychiatric assessment, the Schedules for Clinical Assessment in Neuropsychiatry (SCAN 2.1).
3. Patients included must have prominent negative symptoms and patients must have a negative subscore = or > than 15 on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS).
4. Only patients who are fully capable of making their own decision regarding participation in the research will be included.
|- Exclusion criteria||1. Exclusion criteria include rTMS and MRI contraindications (e.g. a personal or family history of epileptic seizures, history of brain surgery, intracerebral or pacemaker implants, inner ear prosthesis or other metal prosthetics/implants). |
2. Neurological disorders, a head injury with loss of consciousness in the past.
3. Substance dependency within the previous 6 months.
4. Previous treatment with rTMS.
5. Severe behavioural disorders.
6. Inability to provide informed consent.
8. Female patients who are pregnant will be excluded.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mei-2008|
|- planned closingdate||1-mei-2012|
|- Target number of participants||32|
|- Interventions||The rTMS group of 16 patients will receive bilateral high frequency rTMS stimulation during 15 days, sessions being given twice daily. |
The sham group of 16 patients will constitute the placebo group and receive 15 days of bilateral sham stimulation twice daily.
|- Primary outcome||The primary outcome of the study is a significant decline of negative symptoms and cognitive dysfunctioning after bilateral high frequency rTMS treatment of the DLPFC.|
|- Secondary outcome||The secondary outcome of the study is increased cortical activation in the DLPFC after rTMS treatment, measured through a fMRI study. |
|- Timepoints||Follow-up measurements will be done at 4 weeks and 3 months|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||Drs. J. Dlabac-de Lange|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. A. Aleman|
|- Sponsor/Initiator ||University Medical Center Groningen (UMCG)|
(Source(s) of Monetary or Material Support)
|- Brief summary||Negative symptoms in schizophrenia include anhedonia, avolition, alogia and blunted affect. They predict a worse clinical outcome and are often indicative of poorer social, occupational and global outcomes. Currently, no effective treatment exists to improve negative symptoms. The primary objective of the current investigation is to determine the effectiveness of bilateral high frequency rTMS treatment of the dorsolateral prefrontal cortex (DLPFC) on negative symptoms and cognitive dysfunction in patients with schizophrenia. The secondary objective is to study brain activity and changes in brain activity after rTMS through a fMRI study. |
Design: Double-blind sham controlled study.
Sample size: 32 patients, 16 in the treatment group and 16 in the sham group.
Study population: All patients should be over 18 years old and should meet the diagnostic criteria for schizophrenia, based on the patientís medical file and confirmed by a standardized psychiatric assessment. Inpatients as well as outpatients can participate.
Invervention: The rTMS group of 16 patients will receive bilateral rTMS stimulation during 15 days, sessions being given twice daily. The sham group of 16 patients will constitute the placebo group and receive 15 days of bilateral sham stimulation twice daily. The primary outcome of the study is a significant decline of negative symptoms and cognitive dysfunctioning after bilateral high frequency rTMS treatment of the DLPFC. The secondary outcome of the study is increased cortical activation in the DLPFC after rTMS treatment, measured through a fMRI study.
|- Main changes (audit trail)|
|- RECORD||4-feb-2008 - 28-dec-2012|