Accelerated Neuromodulation Therapy for Negative Symptoms of Schizophrenia (TMSNS)

August 19, 2026 updated by: David Benrimoh, Douglas Mental Health University Institute

Accelerated, Neuronavigated Neuromodulation Therapy for Negative Symptoms of Schizophrenia

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

75

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H1N 3M5
        • Not yet recruiting
        • Institut Universitaire en Santé Mentale de Montréal
        • Principal Investigator:
          • Stéphane Potvin, PhD
        • Contact:
      • Québec, Quebec, Canada, G1J 2G3
        • Not yet recruiting
        • Institut universitaire de santé mentale de Québec - Centre de recherche CERVO
        • Contact:
        • Principal Investigator:
          • Olivier Roy, MD, MSc, PhD, FRCPC
      • Verdun, Quebec, Canada, H4H 1R3
        • Recruiting
        • McGill Lab for Computational Psychiatry and Translation - Burland Pavilion 6875 Boulevard LaSalle Montreal, QC
        • Contact:
        • Principal Investigator:
          • David Benrimoh, MD.CM., MSc., MSc., FRCPC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active iTBS (Neuronavigated Targeting)
Participants receive iTBS over five consecutive days (ten sessions/day) targeting the left dorsolateral prefrontal cortex using neuronavigation-guided targeting.
Device: Neuronavigated 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.
Experimental: Active iTBS (BEAM-F3 Targeting)
Participants receive iTBS over five consecutive days (ten sessions/day) targeting the left dorsolateral prefrontal cortex using BEAM-F3 targeting.
Device: BEAM-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 Comparator: Sham iTBS
Participants receive sham iTBS over five consecutive days (ten sessions/day) using the same session structure and procedures as active treatment.
Device: Sham Intermittent Theta Burst Stimulation

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Avolition/Apathy Subscale Score
Time Frame: 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.
Baseline to 1 week, 1 month, and 3 months post-treatment
Change in Scale for the Assessment of Negative Symptoms Total Score
Time Frame: 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.
Baseline to 1 week, 1 month, and 3 months post-treatment
Change in Brief Negative Symptom Scale Total Score
Time Frame: 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.
Baseline to 1 week, 1 month, and 3 months post-treatment
Effect of Targeting Method on Negative Symptoms
Time Frame: 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.
Baseline to 1 week, 1 month, and 3 months post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Affective Processing
Time Frame: 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.
Baseline to 1 week, 1 month, and 3 months post-treatment
Change in Social Appraisal
Time Frame: 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.
Baseline to 1 week, 1 month, and 3 months post-treatment
Change in Cognitive Performance
Time Frame: 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.
Baseline to 1 week, 1 month, and 3 months post-treatment
Change in Montgomery-Åsberg Depression Rating Scale Score
Time Frame: 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.
Baseline to 1 week, 1 month, and 3 months post-treatment
Change in Calgary Depression Scale for Schizophrenia Score
Time Frame: 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.
Baseline to 1 week, 1 month, and 3 months post-treatment
Change in Social and Occupational Functioning Assessment Scale Score
Time Frame: 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.
Baseline to 1 week, 1 month, and 3 months post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Douglas Mental Health University Institute

Collaborators

Centre de recherche CERVO
Centre de Recherche de l'Institut Universitaire en santé Mentale de Montréal
Magnus Medical

Investigators

  • Principal Investigator: David Benrimoh, MD.CM., MSc., MSc., FRCPC, McGill University, Department of Psychiatry
  • Principal Investigator: Olivier Roy, MD, Centre de recherche CERVO - Université Laval
  • Principal Investigator: Stéphane Potvin, PhD, Institut Universitaire en Santé Mentale de Montréal
  • Principal Investigator: Lena Palaniyappan, MD, PhD, Douglas Mental Health Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2026

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

February 12, 2026

First Submitted That Met QC Criteria

February 19, 2026

First Posted (Actual)

February 23, 2026

Study Record Updates

Last Update Posted (Actual)

August 20, 2026

Last Update Submitted That Met QC Criteria

August 19, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MP-18-2025-1206
  • 8401470ASMQ (Other Grant/Funding Number: Alliance Santé Mentale - Axe Neuromodulation)
  • CIHR-8401550 (Other Grant/Funding Number: CIHR)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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