Schizophrenia and Predominant Negative Symptoms
Conditions
Keywords
Negative symptoms, Neuromodulation therapy, Non-invasive brain stimulation, Accelerated treatment, Schizophrenia spectrum disorders, TMS, Transcranial Magnetic Stimulation, Outpatient treatment
Brief summary
The goal of this clinical trial is to learn if an accelerated form of neuromodulation therapy can help improve negative symptoms of schizophrenia. Negative symptoms can include low motivation, reduced emotional expression, and difficulty with social interaction. The study will also look at how safe and tolerable this treatment is when given over a short period of time. Participants will be randomly assigned to receive either active neuromodulation therapy or sham (placebo) stimulation. The study will also compare two different ways of choosing where to place the stimulation. The investigators want to learn whether this accelerated treatment approach is safe and feasible for people with schizophrenia, whether negative symptoms improve after treatment, and whether the way the stimulation site is chosen affects outcomes Participants will be asked to complete clinical interviews and questionnaires, undergo a brain scan, receive neuromodulation therapy or sham stimulation over five consecutive days, and attend follow-up visits after treatment This study is being conducted at three hospitals in Canada and is designed to help plan larger studies in the future.
Detailed description
Negative symptoms of schizophrenia, including diminished motivation, reduced emotional expression, and impaired social functioning, are a major contributor to long-term disability and remain inadequately treated by existing interventions. Repetitive transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex has demonstrated potential benefit for negative symptoms, but conventional treatment schedules often require multiple weeks of daily sessions, which may limit feasibility in this population. Accelerated neuromodulation therapy delivers multiple stimulation sessions per day over a condensed time period and may improve accessibility, adherence, and tolerability. This pilot study evaluates an accelerated iTBS protocol delivered over five consecutive days in individuals with schizophrenia spectrum disorders who exhibit clinically significant negative symptoms. Participants are randomized to receive either active neuromodulation therapy or sham stimulation. In addition, the study evaluates two approaches to stimulation targeting. Targeting approach is assigned according to study procedures designed to preserve participant and rater blinding. All participants undergo baseline clinical, behavioral, and functional assessments, followed by the accelerated treatment protocol and post-treatment follow-up assessments. Primary outcomes focus on changes in negative symptom severity, while secondary outcomes assess depressive symptoms, functional outcomes, and task-based behavioral measures.
Interventions
DEVICENeuronavigated Intermittent Theta Burst Stimulation
Neuronavigated intermittent theta burst stimulation (iTBS) is delivered using a transcranial magnetic stimulation device with a figure-of-eight coil targeting the left dorsolateral prefrontal cortex. Individualized stimulation targets are identified using functional MRI data and are imported into a neuronavigation system to guide coil positioning and orientation throughout treatment. Treatment is delivered over five consecutive days using an accelerated schedule consisting of ten stimulation sessions per day. Each iTBS session is delivered at an intensity corresponding to 110% of the participant's resting motor threshold, with stimulation intensity adjusted for individual cortical depth.
DEVICEBEAM-F3 Intermittent theta burst stimulation
BEAM-F3 intermittent theta burst stimulation (iTBS) is delivered using a transcranial magnetic stimulation device with a figure-of-eight coil targeting the left dorsolateral prefrontal cortex. Stimulation targets are identified according to the BEAM-F3 procedure. Treatment is delivered over five consecutive days using an accelerated schedule consisting of ten stimulation sessions per day. Each iTBS session is delivered at an intensity corresponding to 110% of the participant's resting motor threshold, with stimulation intensity adjusted for individual cortical depth.
Sham intermittent theta burst stimulation is delivered using a transcranial magnetic stimulation device with a figure-of-eight coil positioned over the left dorsolateral prefrontal cortex. Coil placement, session structure, and treatment schedule are identical to those used for active stimulation. Treatment is delivered over five consecutive days using an accelerated schedule consisting of ten stimulation sessions per day. Sham stimulation is administered using procedures designed to mimic the experience of active iTBS without producing therapeutic cortical stimulation.
Sponsors
Douglas Mental Health University Institute
Centre de recherche CERVO
Magnus Medical
Centre de Recherche de l'Institut Universitaire en santé Mentale de Montréal
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
Participants, outcome assessors and treaters are blinded to treatment assignment. Care providers are blinded where feasible based on study procedures. Measures are in place to preserve blinding throughout the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder * Duration of illness ≥ 6 months * Clinically significant negative symptoms * Must have been on a stable pharmacological treatment for at least 4 weeks before entering the study * Clinicians will confirm that patients' negative and positive symptoms have been stable per their clinical opinion for at least 3 months. * Participants must be able to provide informed consent * Ability to undergo MRI scanning
Exclusion criteria
* Pregnancy, lactation, or an intrauterine device * History of electroconvulsive therapy (ECT) in the past 6 months * Use of licit or illicit substances (excluding cannabis) during the week of treatment and in the 24 hours prior to fMRI scans * Contraindications for TMS * Previous treatment with rTMS * Documented history of significant intellectual disability * Primary diagnosis of psychotic disorder secondary to a medical condition or substance-induced psychosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Avolition/Apathy Subscale Score | Baseline to 1 week, 1 month, and 3 months post-treatment | Change in score on the Avolition/Apathy subscale of the Scale for the Assessment of Negative Symptoms (SANS). The SANS Avolition/Apathy subscale ranges from 0 to 25, with higher scores indicating greater negative symptom severity. |
| Change in Scale for the Assessment of Negative Symptoms Total Score | Baseline to 1 week, 1 month, and 3 months post-treatment | Change in total score on the Scale for the Assessment of Negative Symptoms (SANS). Total scores range from 0 to 125, with higher scores indicating greater negative symptom severity. |
| Change in Brief Negative Symptom Scale Total Score | Baseline to 1 week, 1 month, and 3 months post-treatment | Change in total score on the Brief Negative Symptom Scale (BNSS). Total scores range from 0 to 78, with higher scores indicating greater negative symptom severity. |
| Effect of Targeting Method on Negative Symptoms | Baseline to 1 week, 1 month, and 3 months post-treatment | Difference in change in negative symptom severity between targeting methods, as measured by negative symptom outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Calgary Depression Scale for Schizophrenia Score | Baseline to 1 week, 1 month, and 3 months post-treatment | Change in score on the Calgary Depression Scale for Schizophrenia. Total scores range from 0 to 27, with higher scores indicating greater depressive symptom severity. |
| Change in Affective Processing | Baseline to 1 week, 1 month, and 3 months post-treatment | Change in affective processing as measured by performance on a behavioural task assessing conditioned hallucinations related to valenced auditory information. |
| Change in Social and Occupational Functioning Assessment Scale Score | Baseline to 1 week, 1 month, and 3 months post-treatment | Change in score on the Social and Occupational Functioning Assessment Scale. Scores range from 0 to 100, with higher scores indicating better functioning. |
| Change in Social Appraisal | Baseline to 1 week, 1 month, and 3 months post-treatment | Change in social appraisal and belief updating as measured by performance on a behavioral task assessing social inference and valuation. |
| Change in Cognitive Performance | Baseline to 1 week, 1 month, and 3 months post-treatment | Change in cognitive performance as measured by an automated cognitive battery assessing attention, processing speed, working memory, verbal memory, verbal fluency, and executive function. |
| Change in Montgomery-Åsberg Depression Rating Scale Score | Baseline to 1 week, 1 month, and 3 months post-treatment | Change in score on the Montgomery-Åsberg Depression Rating Scale. Total scores range from 0 to 60, with higher scores indicating greater depressive symptom severity. |
Countries
Canada
Contacts
CONTACTAshley S. Choucroun
PRINCIPAL_INVESTIGATORDavid Benrimoh, MD.CM., MSc., MSc., FRCPC
McGill University, Department of Psychiatry
PRINCIPAL_INVESTIGATOROlivier Roy, MD
Centre de recherche CERVO - Université Laval
PRINCIPAL_INVESTIGATORStéphane Potvin, PhD
Institut Universitaire en Santé Mentale de Montréal
PRINCIPAL_INVESTIGATORLena Palaniyappan, MD, PhD
Douglas Mental Health Institute
Outcome results
None listed