Clinical trial NCT02905604: Magnetic Stimulation of the Brain in Schizophrenia or Depression
Official title: Magnetic Stimulation of the Brain in Schizophrenia or Depression: A Randomized, Double Blind, Sham Controlled Trial of Repetitive Transcranial Magnetic Stimulation in Schizophrenia or Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Depression
Anhedonia
Avolition
Keywords: rTMS
negative symptoms
intermittent theta burst
iTBS
repetitive transcranial magnetic stimulation
dorsomedial prefrontal cortex
dmPFC
NIRS
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2016-09-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to evaluate if repetitive transcranial magnetic stimulation (rTMS) with theta burst frequency over dorsomedial prefrontal cortex (DMPFC) is an effective treatment for negative symptoms (anhedonia and avolition) in schizophrenia or depression. Other objectives are to increase the understanding of the underlying neurobiology of negative symptoms and the mechanisms for the treatment effect of rTMS.

Detailed description: This is a double blind parallel randomized sham controlled trial. The intervention is intermittent theta-burst stimulation (iTBS), which is rTMS with theta burst frequency with 2400 pulses/day in two sessions at 90% of resting motor threshold intensity over the DMPFC, given in ten days on week days (10 treatment days must be completed within a maximum of 21 days). Stratified (depression and schizophrenia diagnosis) block randomization will be used for treatment allocation to active or sham side of the stimulation coil.

Patients will be referred from their regular psychiatric care facilities. At the screening visit the patient will be assessed if fulfilling all inclusion and none of the exclusion criteria. At the baseline visit thorough psychiatric, cognitive and neurophysiological examination will be performed. The latter include investigation of cortical excitability with paired-pulse TMS, mismatch negativity (MMN, a measure of aberrant stimulus detection), startle-response, habituation, electrodermal activity (EDA), near-infrared spectroscopy (NIRS), 24 hour actigraphy and heart rate registration.

During 10 week days the participants will receive a daily rTMS (or sham) treatment. On the day after last rTMS treatment the examinations performed at the baseline visit will be repeated. Four weeks after baseline there is a shorter visit to follow-up symptoms and functioning. At the end of this visit the blinding is unmasked and patients who have received sham rTMS will be offered active treatment in an open-phase. After the four weeks follow-up there are two additional and identical visits at 10 and 26 weeks after start of treatment.

Eligibility criteria: Inclusion Criteria:

* diagnosis of schizophrenia spectrum disorders or uni- or bipolar depression verified through a Mini International Neuropsychiatric Interview (M.I.N.I.)
* negative symptoms with anhedonia and avolition: ≤40 points on the The Motivation and Pleasure Scale-Self-Report (MAP-SR)
* unchanged medication the past month
* provision of signed informed consent form

Exclusion Criteria:

* epilepsy
* conductive ferromagnetic or other magnetic sensitive metals implanted in the head or within 30 cm of the treatment coil
* implanted device that is activated or controlled in any way by physiological signals
* implanted mediation pumps
* intracardiac lines, even when removed
* addiction (illicit drugs or alcohol) and pregnancy
* any condition that seriously increases the risk of non-compliance or loss of follow-up

Primary outcomes:
measure: Mean change of total score on the Clinical Assessment Interview for Negative Symptoms (CAINS).
timeFrame: From baseline to day after last treatment, i.e. 14-21 days after baseline
Secondary outcomes:
measure: Mean change of total score on the CAINS
timeFrame: From baseline to four weeks after baseline.
measure: Change in Clinical Global Impression (CGI) score
timeFrame: From baseline to four weeks after baseline.
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trials
Study officials:
affiliation: Uppsala University
name: Robert Bodén, Ph.D, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Malm E, Struckmann W, Persson J, Boden R. Pain trajectories of dorsomedial prefrontal intermittent theta burst stimulation versus sham treatment in depression. BMC Neurol. 2020 Aug 20;20(1):311. doi: 10.1186/s12883-020-01881-3.