Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Magnetic Seizure Therapy (MST) for Treatment Resistant Depression, Schizophrenia, and Obsessive Compulsive Disorder

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University Health Network, Toronto
Information provided by (Responsible Party):
Z. J. Daskalakis, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT01596608
First received: May 8, 2012
Last updated: October 3, 2014
Last verified: April 2014
  Purpose

Electroconvulsive therapy (ECT) has unparalleled efficacy in treating severe depression, and is also useful in treatment-refractory cases of schizophrenia and obsessive compulsive disorder (OCD). However, its use is limited by significant adverse effects on memory and cognition. In addition, ECT cannot be precisely targeted, since it relies on unpredictable pathways of electrical conduction through the brain. Magnetic seizure therapy (MST) is currently under investigation as a targetable, cognition-sparing alternative to ECT. MST uses magnetic fields rather than electrical stimuli for seizure induction, dramatically reducing the passage of induced current through undesired brain regions. 10 years of experimental studies have established the safety of MST in animal and human subjects. This pilot study will investigate whether MST has similar efficacy to ECT, with fewer cognitive side effects, in patients with severe depression, schizophrenia, and OCD.


Condition Intervention
Depressive Disorder
Schizophrenia
Schizoaffective Disorder
Obsessive-Compulsive Disorder
Device: Magnetic Seizure Therapy (MagPro MST)

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy and Tolerability of Magnetic Seizure Therapy (MST) as an Alternative to Electroconvulsive Therapy (ECT) for Treatment Resistant Depression, Schizophrenia, and Obsessive Compulsive Disorder

Resource links provided by NLM:


Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • Score on rating scale that corresponds to diagnosis: i) Hamilton Rating Scale for Depression, 24-item (HRSD-24); or ii) Yale-Brown Obsessive Compulsive Scale (Y-BOCS); or iii) Brief Psychiatric Rating Scale (BPRS) [ Time Frame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at date of symptom remission or date of the 24th treatment, whichever comes first, assessed up to 12 weeks ] [ Designated as safety issue: No ]

    i) The HRSD-24 is a semi-structured, clinician-administered scale used to assessed the severity of depressive symptoms.

    ii) The Y-BOCS is a clinician-rated scale used to assess the severity of OCD symptoms.

    iii) The BPRS is a clinician-administered scale used to assess the severity of various psychiatric symptoms, such as depression, anxiety, hallucinations, and delusions. In this study, it will be used with participants diagnosed with schizophrenia.


  • Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS [ Time Frame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 1 month after final treatment ] [ Designated as safety issue: No ]
  • Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS [ Time Frame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 2 months after final treatment ] [ Designated as safety issue: No ]
  • Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS [ Time Frame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 3 months after final treatment ] [ Designated as safety issue: No ]
  • Score on rating scale that corresponds to diagnosis: i) HRSD-24; or ii) Y-BOCS; or iii) BPRS [ Time Frame: Change from baseline in HRSD-24 / Y-BOCS / BPRS at 6 months after final treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cognitive Functioning [ Time Frame: Change from baseline in cognitive functioning at date of symptom remission or at date of 24th treatment, whichever comes first, assessed up to 12 weeks ] [ Designated as safety issue: Yes ]
    Improvement or sparing of cognitive functioning, as assessed by standard tests of episodic memory and non-memory cognitive functions.

  • Cognitive Functioning [ Time Frame: Change from baseline in cognitive functioning at 6 months after final treatment ] [ Designated as safety issue: Yes ]
  • Neuroimaging (brain structure and activity) [ Time Frame: Changes from baseline in brain structure and activity within 48 hours after final treatment ] [ Designated as safety issue: No ]
    Improvements in cortical thickness in subgenual cingulate cortex on T1 MRI voxel-based morphometry; improved anatomical connectivity between anterior hippocampus, subgenual cingulate cortex, and retrosplenial cortex on voxel-based comparative DTI tractography; subgenual and orbitofrontal functional connectivity to amygdala and ventral striatum on T2* fMRI BOLD signal covariation.

  • Neuroimaging (brain structure and activity) [ Time Frame: Changes from baseline in brain structure and activity at 6 months after final treatment ] [ Designated as safety issue: No ]
    Improvements in cortical thickness in subgenual cingulate cortex on T1 MRI voxel-based morphometry; improved anatomical connectivity between anterior hippocampus, subgenual cingulate cortex, and retrosplenial cortex on voxel-based comparative DTI tractography; subgenual and orbitofrontal functional connectivity to amygdala and ventral striatum on T2* fMRI BOLD signal covariation.


Estimated Enrollment: 60
Study Start Date: February 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Magnetic Seizure Therapy Device: Magnetic Seizure Therapy (MagPro MST)
100% machine output at between 50 and 100 Hz, with coil directed over frontal brain regions, until adequate seizure achieved. Six treatment sessions, at a frequency of two or three times per week will be administered. If subjects fail to achieve the pre-defined criteria of remission at that point, the dose will be increased to the maximal stimulator output and 3 additional treatment sessions will be provided. This will be repeated a total of 5 times (i.e., maximum treatment number is 24). 24 treatments is typically longer that a conventional ECT treatment course. However, evidence does suggest that longer treatment courses may be needed with MST, particularly in more treatment resistant psychiatric conditions such as OCD and schizophrenia.
Other Name: MagPro MST (Tonica Elektronik A/S, Denmark)

Detailed Description:

Although ECT is effective against severe depression, psychosis, and OCD, it also produces significant impairments of autobiographical memory and other cognitive functions. These side effects limit the acceptability and tolerability of ECT in many patient populations. They also limit the number of treatments that can be administered in a course of ECT, leading to high relapse rates once ECT is discontinued. In animal studies, MST has been shown to have far fewer adverse cognitive effects than ECT. In small human studies, humans have shown faster subjective and objective recovery of orientation after MST than with ECT. However, the precise degree of cognitive sparing in MST versus ECT has yet to be established. Likewise, the comparative efficacy of MST versus ECT in severe depression, schizophrenia, and OCD remains to be seen. The investigators aim to determine whether MST spares autobiographical memory and other cognitive functions, while retaining comparable efficacy to that of ECT.

Objective 1: To compare the efficacy of MST and ECT in treating patients with severe depression, schizophrenia, and OCD.

Hypothesis 1: MST will have equivalent efficacy to ECT on objective measures of mood, schizophrenia, and OCD symptoms.

Objective 2: To compare the effects of MST and ECT on autobiographical memory and other cognitive functions in patients with severe depression, schizophrenia, schizoaffective disorder and OCD.

Hypothesis 2: MST will have significantly lower adverse effects on objective measures of autobiographical memory and other cognitive functions in patients with severe depression, schizophrenia, and OCD.

Objective 3: To compare the changes in brain function that result from MST and ECT.

Hypothesis 3: Both MST and ECT will produce changes in functional brain activity consistent with antidepressant response, antipsychotic response, and antiobsessive response, along with a sparing of cognitive functions.

The discovery of a viable alternative to ECT, with equivalent efficacy but fewer side effects, would have a transformative effect on the treatment of several forms of severe mental illness. At present, many patients who could benefit from ECT do not pursue this treatment due to concerns about cognitive side effects, as well as the enduring social stigma of ECT itself. In addition, many patients who have benefited from ECT are obliged to discontinue this effective treatment because of mounting cognitive side effects; high rates of relapse then ensue.

If MST could be shown to spare autobiographical memory and other forms of cognition, many more patients would be willing to take advantage of the treatment. They would also be able to continue the treatment, when effective, for longer periods. The potential result would be a dramatic improvement in the rates of remission and relapse for patients with severe depression and other forms of mental illness.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ages 18 to 85
  • DSM-IV diagnosis of major depressive episode with or without psychotic features in the context of MDD or bipolar disorder; OCD or Schizophrenia
  • 24-item HRSD score of ≥ 21 (for depression subjects)
  • 18-item BPRS score of ≥ 37 (for schizophrenia subjects)
  • Y-BOCS score of ≥ 16 (for OCD subjects)
  • demonstrate capacity to give informed consent
  • are a Canadian resident

Exclusion Criteria:

  • have an unstable medical and/or neurological condition
  • are currently pregnant or lactating
  • are not considered sufficiently well to undergo general anesthesia for any reason
  • have a cardiac pacemaker, cochlear implant, implanted electronic device or non-electric metallic implant
  • are taking a benzodiazepine at a dose greater than lorazepam 2mg or equivalent
  • are taking any non-benzodiazepine anticonvulsant
  • have active substance misuse or dependence within the past 3 months
  • have a current diagnosis of delirium, dementia or another cognitive disorder secondary to a general medical condition
  • have a co-morbid borderline personality disorder and/or antisocial personality disorder
  • have had a history of any suicide attempts in the past 6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01596608

Locations
Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M6J 1H4
Sponsors and Collaborators
Centre for Addiction and Mental Health
University Health Network, Toronto
Investigators
Principal Investigator: Z. Jeffrey Daskalakis, MD, PhD. Centre for Addiction and Mental Health
  More Information

Additional Information:
No publications provided

Responsible Party: Z. J. Daskalakis, Chair, Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01596608     History of Changes
Other Study ID Numbers: 145-2010
Study First Received: May 8, 2012
Last Updated: October 3, 2014
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
Magnetic seizure therapy
Treatment resistance
Open-label trial
Treatment resistant depression
Treatment resistant schizophrenia
Treatment resistant obsessive-compulsive disorder

Additional relevant MeSH terms:
Compulsive Personality Disorder
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Disease
Obsessive-Compulsive Disorder
Psychotic Disorders
Schizophrenia
Seizures
Anxiety Disorders
Behavioral Symptoms
Brain Diseases
Central Nervous System Diseases
Epilepsy
Mental Disorders
Mood Disorders
Nervous System Diseases
Neurologic Manifestations
Pathologic Processes
Personality Disorders
Schizophrenia and Disorders with Psychotic Features
Signs and Symptoms

ClinicalTrials.gov processed this record on November 23, 2014