Magnetic Stimulation of the Brain in Schizophrenia or Depression

NCT ID: NCT02905604

Last Updated: 2020-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-29
• Study Completion Date: 2020-01-20

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.

Conditions

Schizophrenia; Depression; Anhedonia; Avolition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

dmPFC iTBS

Intervention Type: DEVICE

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

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.

Group Type: SHAM_COMPARATOR

dmPFC Sham iTBS

Intervention Type: DEVICE

Sham iTBS

Interventions

dmPFC iTBS

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

Intervention Type: DEVICE

dmPFC Sham iTBS

Sham iTBS

Intervention Type: DEVICE

Other Intervention Names

rTMS with intermittent theta-burst frequency

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Uppsala University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Bodén, Ph.D, MD

Role: PRINCIPAL_INVESTIGATOR

Uppsala University

Locations

Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trials

Uppsala, , Sweden

Countries

Sweden

References

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.

Reference Type: DERIVED

PMID: 32819321 (View on PubMed)

Other Identifiers

MA-SCH-DEP

Identifier Type: -

Identifier Source: org_study_id