SchizophreniaModSoCCSNCT04418011
Neuromodulation of Social Cognitive Circuitry in People With Schizophrenia Spectrum Disorders
A study testing Repetitive Transcranial Magnetic Stimulation and Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation) in people with Schizophrenia and Schizoaffective Disorder, run by Centre for Addiction and Mental Health at 3 sites in 2 countries.
Trial summary
In this study, the investigators will be examining the effects of repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) on social cognitive impairments in individuals with schizophrenia spectrum disorders. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorders
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation and Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 30 Nov 2020to 2 Feb 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-55 years;
- Male or Female;
- DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder; other specified psychotic disorder (documented by SCID-5);
- Prescription of antipsychotic medication for at least 60 days and constant dose for 30 days prior to study entry (either first or second generation antipsychotics permitted);
- Able to participate in the informed consent process and provide voluntary informed consent.
Who cannot join
- DSM-5 substance use disorder (other than caffeine, mild cannabis use, or tobacco) within the past six months; or a positive baseline urine drug screen (except cannabis for mild use). Only participants meeting a moderate to severe cannabis use disorder will be excluded
- Type 1 diabetes mellitus (i.e., insulin-dependent diabetes mellitus with onset < 35 years of age and/or diabetes mellitus that has been complicated by a prior documented episode of ketoacidosis)
- Acute or unstable medical illness (e.g. delirium, cancer, uncontrolled diabetes, decompensated cardiac, hepatic, renal or pulmonary disease, stroke, or myocardial infarction), whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol
- Neurological disease associated with extrapyramidal signs and symptoms (e.g. Parkinson's disease); epilepsy (i.e. seizures not due to medication/drugs or due to fever) or physical signs of stroke; any diagnosis of a Central Nervous System (CNS) disorder
- Requires a benzodiazepine with a regular dose equivalent to lorazepam 2 mg/day or higher or any anticonvulsant due to the potential of these medications to limit the efficacy of rTMS
- Suspected DSM-5 intellectual disability based upon clinical interview and psychosocial history or estimated IQ of <71
Show all 11Show fewer
- Prior Psychosurgery
- Presence of MRI contraindications (e.g. pacemakers)
- Pregnancy (self-report)
- rTMS treatment in the last 5 years
- Non-English speakers
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Maryland Psychiatric Research Centre
Catonsville, Maryland, 21228
The Feinstein Institute for Medical Research
Manhasset, New York, 11030
About this study
In this study, the investigators will be examining the effects of repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) on social cognitive impairments in individuals with schizophrenia spectrum disorders. Participants will be chosen by chance to receive either active rTMS stimulation, active iTBS stimulation, sham rTMS, or sham iTBS. The investigators predict that active 10Hz and iTBS stimulation will improve social cognitive impairments compared to sham stimulation. We aim to identify which type of active stimulation is most effective at inducing changes social cognition brain circuitry and secondarily which type of active stimulation is best tolerated and most effective at inducing changes in social cognitive performance.
Read the detailed description
This study is a randomized, double blind, sham controlled study which aims to use repetitive transcranial magnetic stimulation (rTMS), a form of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with Schizophrenia Spectrum Disorders. We will randomize 60 people with SSDs to three groups: 20 to a conventional form of rTMS (i.e. 10 Hz rTMS); 20 to intermittent theta burst stimulation (iTBS); and 20 to either sham 10Hz rTMS stimulation or sham iTBS. We will determine whether these treatments can change the functional connectivity of key SCog brain circuits by targeting a brain region known as the dorsomedial prefrontal cortex (DMPFC). Since each person's anatomical and functional brain profile is slightly different, we will optimize the orientation and location of coil placement in each individual. Overall, our proposal follows a target engagement framework, including specifics regarding testing brain stimulation parameters (i.e., rTMS vs. iTBS) and individualizing coil placement for optimal targeting. We anticipate that active 10 Hz rTMS or iTBS will demonstrate target engagement compared to sham, and potentially ameliorate SCog deficits in people with SSDs. Our primary goal is to identify which treatment best induces change in SCog brain circuitry and secondarily which treatment is best tolerated and induces changes in social cognitive performance.
- Being tested
- Repetitive Transcranial Magnetic Stimulation, Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation), Repetitive Transcranial Magnetic Stimulation (Sham)
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic StimulationDevice
The present study aims to use both repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), safe and effective forms of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with SSDs. Treatment sessions will be administered five days per week for two weeks.
Other Name: MagPro X100 or R30 (Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)
Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation)Device
The present study aims to use both repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), safe and effective forms of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with SSDs. Treatment sessions will be administered five days per week for two weeks.
Other Name: MagPro X100 or R30 (Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)
Repetitive Transcranial Magnetic Stimulation (Sham)Device
Other Name: MagPro X100 or R30(Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)
| Study group | Role | What they receive |
|---|---|---|
| Active 10 Hz rTMS | Active comparator | Active treatment will be targeted to an intensity that is 120% of the resting motor threshold. Stimulation will be delivered at 10 Hz according to conventional FDA-approved parameters (4 s on and 26 s off; 3000 pulses per session; total duration 37.5 mins) . Receives: Device: Repetitive Transcranial Magnetic Stimulation |
| Active iTBS | Active comparator | Active iTBS will be targeted to an intensity that is 120% of the resting motor threshold. Stimulation will be delivered in triplet 50 Hz bursts, repeated at 5 Hz; 2 seconds on and 8 seconds off; 600 pulses per session; total duration of 3 min 9 seconds. Receives: Device: Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation) |
| Sham rTMS | Sham comparator | Sham stimulation will be delivered using the same stimulation parameters as either 10 Hz rTMS or iTBS.
For both active and sham stimulation, TMS coil positioning for each individual will be optimized by combining participant fMRI data, meta-analytic functional analysis, electric field modelling, and real-time neuronavigation. Receives: Device: Repetitive Transcranial Magnetic Stimulation (Sham) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mentalizing brain network functional connectivity
Measured using the empathic accuracy fMRI task
Measured: 2 weeks
Secondary outcomes (4)
Treatment Tolerability
Measured using the Visual Analogue Scale for Pain (VAS)
Measured: 2 weeks
Treatment Tolerability
Measured using proportion of participants that report headache
Measured: 2 weeks
Treatment Tolerability
Measured using proportion of participants that report dizziness
Measured: 2 weeks
Treatment Tolerability
Measured using proportion of treatment related SAE's
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2020
- Study start30 Nov 2020
- Primary completion2 Feb 2023
- Study completion2 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Northwell Health, University of Maryland, Baltimore, National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Aristotle Voineskos, MD, Principal investigator, Centre for Addiction and Mental HealthAnil Malhotra, MD, Principal investigator, The Feinstein Institute for Medical Research, Zucker Hillside HospitalRobert Buchanan, MD, Principal investigator, Maryland Psychiatric Research Centre, University of Maryland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04418011
- Sponsor's protocol ID
- 133/2019
- Acronym
- ModSoCCS
- Status last verified
- Oct 2023
- First submitted
- 5 May 2020
- Last updated
- 17 Oct 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes
Publications
Oliver LD, Blumberger DM, Deng ZD, Hawco C, Dickie EW, Gallucci J, Jeyachandra J, Mansour S, Hare SM, Gold JM, Foussias G, Argyelan M, Daskalakis ZJ, Buchanan RW, Malhotra AK, Voineskos AN. Effects of personalized transcranial magnetic stimulation on social cognitive network functional connectivity in schizophrenia spectrum disorders: A double-blind, randomized, sham-controlled target engagement trial. Brain Stimul. 2026 Jul 29;19(5):103172. doi: 10.1016/j.brs.2026.103172. Online ahead of print.
PubMed 42526755
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuromodulation of Social Cognitive Circuitry in People With Schizophrenia Spectrum Disorders
- ClinicalTrials.gov ID
- NCT04418011
- Acronym / sponsor ID
- ModSoCCS / 133/2019
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Northwell Health, University of Maryland, Baltimore, National Institutes of Health (NIH)
- Study start
- 30 Nov 2020 (actual)
- Primary completion
- 2 Feb 2023 (actual)
- Study completion
- 2 Feb 2023 (actual)
- First posted
- 5 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, the investigators will be examining the effects of repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) on social cognitive impairments in individuals with schizophrenia spectrum disorders. Participants will be chosen by chance to receive either active rTMS stimulation, active iTBS stimulation, sham rTMS, or sham iTBS. The investigators predict that active 10Hz and iTBS stimulation will improve social cognitive impairments compared to sham stimulation. We aim to identify which type of active stimulation is most effective at inducing changes social cognition brain circuitry and secondarily which type of active stimulation is best tolerated and most effective at inducing changes in social cognitive performance.
Detailed description
This study is a randomized, double blind, sham controlled study which aims to use repetitive transcranial magnetic stimulation (rTMS), a form of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with Schizophrenia Spectrum Disorders. We will randomize 60 people with SSDs to three groups: 20 to a conventional form of rTMS (i.e. 10 Hz rTMS); 20 to intermittent theta burst stimulation (iTBS); and 20 to either sham 10Hz rTMS stimulation or sham iTBS. We will determine whether these treatments can change the functional connectivity of key SCog brain circuits by targeting a brain region known as the dorsomedial prefrontal cortex (DMPFC). Since each person's anatomical and functional brain profile is slightly different, we will optimize the orientation and location of coil placement in each individual. Overall, our proposal follows a target engagement framework, including specifics regarding testing brain stimulation parameters (i.e., rTMS vs. iTBS) and individualizing coil placement for optimal targeting. We anticipate that active 10 Hz rTMS or iTBS will demonstrate target engagement compared to sham, and potentially ameliorate SCog deficits in people with SSDs. Our primary goal is to identify which treatment best induces change in SCog brain circuitry and secondarily which treatment is best tolerated and induces changes in social cognitive performance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Active 10 Hz rTMS | Active comparator | Device: Repetitive Transcranial Magnetic StimulationActive treatment will be targeted to an intensity that is 120% of the resting motor threshold. Stimulation will be delivered at 10 Hz according to conventional FDA-approved parameters (4 s on and 26 s off; 3000 pulses per session; total duration 37.5 mins) . |
| Active iTBS | Active comparator | Device: Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation)Active iTBS will be targeted to an intensity that is 120% of the resting motor threshold. Stimulation will be delivered in triplet 50 Hz bursts, repeated at 5 Hz; 2 seconds on and 8 seconds off; 600 pulses per session; total duration of 3 min 9 seconds. |
| Sham rTMS | Sham comparator | Device: Repetitive Transcranial Magnetic Stimulation (Sham)Sham stimulation will be delivered using the same stimulation parameters as either 10 Hz rTMS or iTBS. For both active and sham stimulation, TMS coil positioning for each individual will be optimized by combining participant fMRI data, meta-analytic functional analysis, electric field modelling, and real-time neuronavigation. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age 18-55 years;
- Male or Female;
- DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder; other specified psychotic disorder (documented by SCID-5);
- Prescription of antipsychotic medication for at least 60 days and constant dose for 30 days prior to study entry (either first or second generation antipsychotics permitted);
- Able to participate in the informed consent process and provide voluntary informed consent.
Key exclusion criteria (11 listed)
- DSM-5 substance use disorder (other than caffeine, mild cannabis use, or tobacco) within the past six months; or a positive baseline urine drug screen (except cannabis for mild use). Only participants meeting a moderate to severe cannabis use disorder will be excluded
- Type 1 diabetes mellitus (i.e., insulin-dependent diabetes mellitus with onset < 35 years of age and/or diabetes mellitus that has been complicated by a prior documented episode of ketoacidosis)
- Acute or unstable medical illness (e.g. delirium, cancer, uncontrolled diabetes, decompensated cardiac, hepatic, renal or pulmonary disease, stroke, or myocardial infarction), whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol
- Neurological disease associated with extrapyramidal signs and symptoms (e.g. Parkinson's disease); epilepsy (i.e. seizures not due to medication/drugs or due to fever) or physical signs of stroke; any diagnosis of a Central Nervous System (CNS) disorder
- Requires a benzodiazepine with a regular dose equivalent to lorazepam 2 mg/day or higher or any anticonvulsant due to the potential of these medications to limit the efficacy of rTMS
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repetitive Transcranial Magnetic StimulationThe present study aims to use both repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), safe and effective forms of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with SSDs. Treatment sessions will be administered five days per week for two weeks. Other Name: MagPro X100 or R30 (Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany) | Device | Active 10 Hz rTMS |
| Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation)The present study aims to use both repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), safe and effective forms of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with SSDs. Treatment sessions will be administered five days per week for two weeks. Other Name: MagPro X100 or R30 (Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany) | Device | Active iTBS |
| Repetitive Transcranial Magnetic Stimulation (Sham)Other Name: MagPro X100 or R30(Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany) | Device | Sham rTMS |
Primary outcome
Change in mentalizing brain network functional connectivity
Time frame: 2 weeks
Measured using the empathic accuracy fMRI task
4 secondary outcomes
Treatment Tolerability
Time frame: 2 weeks
Treatment Tolerability
Time frame: 2 weeks
Treatment Tolerability
Time frame: 2 weeks
Treatment Tolerability
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2023.
- Derived from this study: PubMed 42526755Oliver LD, Blumberger DM, Deng ZD, Hawco C, Dickie EW, Gallucci J, Jeyachandra J, Mansour S, Hare SM, Gold JM, Foussias G, Argyelan M, Daskalakis ZJ, Buchanan RW, Malhotra AK, Voineskos AN. Effects of personalized transcranial magnetic stimulation on social cognitive network functional connectivity in schizophrenia spectrum disorders: A double-blind, randomized, sham-controlled target engagement trial. Brain Stimul. 2026 Jul 29;19(5):103172. doi: 10.1016/j.brs.2026.103172. Online ahead of print.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aristotle Voineskos, MD principal investigator
Centre for Addiction and Mental Health
Anil Malhotra, MD principal investigator
The Feinstein Institute for Medical Research, Zucker Hillside Hospital
Robert Buchanan, MD principal investigator
Maryland Psychiatric Research Centre, University of Maryland
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation and Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation) in people with Schizophrenia and Schizoaffective Disorder, run by Centre for Addiction and Mental Health at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in mentalizing brain network functional connectivity (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04418011, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2023.