MA-SCH-DEP: Magnetic Stimulation of the Brain in Schizophrenia or Depression

Sponsor

Uppsala University (Other)

Overall Status

Completed

CT.gov ID

NCT02905604

Collaborator

(none)

Enrollment

Location

Arms

39.7

Actual Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Depression Anhedonia Avolition	Device: dmPFC iTBS Device: dmPFC Sham iTBS	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 29, 2016

Actual Primary Completion Date :

Dec 1, 2019

Actual Study Completion Date :

Jan 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dmPFC iTBS Repetitive transcranial magnet stimulation (rTMS) over the dorsomedial prefrontal cortices at 90% of the resting motor threshold of the foot flexors. The rTMS is given in 20 trains to the left and right dmPFC, respectively. Each train consists of 10 bursts at 5 Hz (theta-frequency), and each burst consists of 3 pulses at 50 Hz. The stimulation is intermittent with 2 seconds of stimulation, 8 seconds off. After a 15 minute break the whole protocol i applied again, resulting in 2400 pulses/day. Treatment is delivered daily at 10 week days.	Device: dmPFC iTBS 2400 pulses/day over 10 week days over bilateral dmPFC using MagPro X100 and the cool D-B80 A/P coil Other Names: rTMS with intermittent theta-burst frequency
Sham Comparator: dmPFC Sham iTBS A sham treatment protocol by using a sham coil with two identical sides where one side give active treatment as described above while on the other side the coil is insulated so very little magnetic energy is delivered. The coil has a built in positioning sensors and a software handling the randomization codes prompts the operator which side of the coil that should be directed towards the patient. Superficial transcutaneous electrical nerve stimulation (TENS) is applied over the stimulation site of the dmPFC synchronous wiht the TMS pulses to further mimic the sensation of the active stimulation.	Device: dmPFC Sham iTBS Sham iTBS

Arm

Intervention/Treatment

Experimental: dmPFC iTBS

Repetitive transcranial magnet stimulation (rTMS) over the dorsomedial prefrontal cortices at 90% of the resting motor threshold of the foot flexors. The rTMS is given in 20 trains to the left and right dmPFC, respectively. Each train consists of 10 bursts at 5 Hz (theta-frequency), and each burst consists of 3 pulses at 50 Hz. The stimulation is intermittent with 2 seconds of stimulation, 8 seconds off. After a 15 minute break the whole protocol i applied again, resulting in 2400 pulses/day. Treatment is delivered daily at 10 week days.

Device: dmPFC iTBS

2400 pulses/day over 10 week days over bilateral dmPFC using MagPro X100 and the cool D-B80 A/P coil

Other Names:

rTMS with intermittent theta-burst frequency

Sham Comparator: dmPFC Sham iTBS

A sham treatment protocol by using a sham coil with two identical sides where one side give active treatment as described above while on the other side the coil is insulated so very little magnetic energy is delivered. The coil has a built in positioning sensors and a software handling the randomization codes prompts the operator which side of the coil that should be directed towards the patient. Superficial transcutaneous electrical nerve stimulation (TENS) is applied over the stimulation site of the dmPFC synchronous wiht the TMS pulses to further mimic the sensation of the active stimulation.

Device: dmPFC Sham iTBS

Sham iTBS

Outcome Measures

Primary Outcome Measures

Mean change of total score on the Clinical Assessment Interview for Negative Symptoms (CAINS). [From baseline to day after last treatment, i.e. 14-21 days after baseline]

Secondary Outcome Measures

Mean change of total score on the CAINS [From baseline to four weeks after baseline.]
Change in Clinical Global Impression (CGI) score [From baseline to four weeks after baseline.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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