SchizophreniaNCT01545999
Paired Associative Stimulation in the Dorsolateral Prefrontal Cortex in Patients With Schizophrenia
A study testing Brain Stimulation via Transcranial Magnetic Stimulation in people with Schizophrenia, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
The purpose of this study is to 1. assess the effect of PAS in schizophrenia in the dorsolateral prefrontal cortex (DLPFC) 2. assess the effect of PAS induced long-term potentiation (LTP) on the performance of patients with schizophrenia on a cognitive task related to DLFPC. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Brain Stimulation via Transcranial Magnetic Stimulation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2012to Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18 or above
- All races and ethnicities.
- Females and males.
- Meet DSM-IV TR criteria for a current diagnosis of schizophrenia or schizoaffective disorder.
- Clinically stable as operationalized by (1) either having not been hospitalized within 3 months or having been hospitalized for 3 months or more prior to assessment, and (2) having had no change in antipsychotic medication dosage within the 4 weeks prior to assessment.
- Willingness and ability to speak English
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- Willingness to provide informed consent
- Corrected visual ability that enables reading of newspaper headlines and corrected hearing capacity that is adequate to respond to a raised conversational voice.
- Age 18 or above
- Willingness and ability to speak English
- Willingness to provide informed consent
- Corrected visual ability that enables reading of newspaper headlines and corrected hearing capacity that is adequate to respond to a raised conversational voice.
Who cannot join
- Meets criteria for a cognitive disorder secondary to a neurological or other medical disorder affecting the central nervous system (for example, multiple sclerosis, history of traumatic brain injury, stroke, untreated hypothyroidism).
- Mini Mental Status Examination score of 17 and less because a subject with a very low MMSE score is unlikely to be able to compete the NP battery.
- Diagnosis of bipolar disorder or current major depressive episode.
- Meets diagnostic criteria for current alcohol or other drug dependence within 6 months of testing
- Electroconvulsive Therapy (ECT) within 6 months of testing.
- Left handedness.
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- Incompetency to consent
- DSM IV TR psychiatric diagnosis except for simple phobias or an adjustment disorder.
- Other neurological disorder affecting central nervous system.
- Psychotropic medication except for sedative /hypnotics at a stable dose for at least 4 weeks.
- Family history of a primary psychotic disorder in a first-degree relative.
- Left handedness.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Paired Associative Stimulation in the Dorsolateral Prefrontal Cortex in Patients With Schizophrenia: a Combined Transcranial Magnetic Stimulation and Electroencephalography Study Across the Life Span
The purpose of this study is to
- assess the effect of PAS in schizophrenia in the dorsolateral prefrontal cortex (DLPFC)
- assess the effect of PAS induced long-term potentiation (LTP) on the performance of patients with schizophrenia on a cognitive task related to DLFPC.
Read the detailed description
Neuroplasticity refers to changes in the strength of communication between different neurons. Long-term potentiation (LTP) is one form of neuroplasticity and refers to the strengthening of such communication. LTP is believed to be a cellular substrate of learning and memory. Paired associative stimulation (PAS) is a transcranial magnetic stimulation (TMS) paradigm that is believed to induce LTP in human subjects. However, its effects have been shown to be minimal in patients with schizophrenia suggesting impaired LTP in schizophrenia. The lack of PAS effect in schizophrenia has been observed in the motor cortex (M1). Thus, the investigators propose to assess the effect of PAS in schizophrenia in the dorsolateral prefrontal cortex (DLPFC), an area of the brain that is especially relevant to learning and memory, and to the pathology in schizophrenia. The investigators also propose to assess the effect of PAS induced LTP on the performance of patients with schizophrenia on a cognitive task that is related to DLFPC.
Hypothesis 1: Patients with schizophrenia will have reduced PAS-LTP in DLPFC in comparison with healthy controls.
Hypothesis 2a: PAS-LTP in patients with schizophrenia and healthy controls randomized to PAS-25 and PAS-100 will correlate with performance on the N-back task at baseline (pre-PAS).
Hypothesis 2b: Healthy controls randomized to PAS-25 will perform better after one session of PAS-25 on the 1- and 7-day N-back task compared to healthy controls randomized to PAS-100.
Hypothesis 2c: Among healthy controls randomized to PAS-25, the magnitude of improvement on the 1- and 7-day N-back task (compared to pre-PAS) that is in excess of the magnitude of improvement on the 1- and 7-day N-back task among subjects randomized to PAS-100 will correlate with the degree of PAS-LTP.
Hypothesis 3a: Patients with schizophrenia who are randomized to receive a 2-week course of PAS-25 will have improved PAS-LTP in DLPFC compared to patients with schizophrenia randomized to 2-week course of PAS-100.
Hypothesis 3b: Patients with schizophrenia who are randomized to receive a 2-week course of PAS-25 will have improved performance on the N-back working memory task compared to patients with schizophrenia randomized to 2-week PAS-100 at 1- and 7-day post-PAS course N-back.
Hypothesis 3c: Patients with schizophrenia who are randomized to receive a 2-week course of PAS-25 will have increased DLPFC cortical thickness compared to patients with schizophrenia randomized to 2-week PAS-100.
Hypothesis 4: Among patients with schizophrenia and healthy controls, PAS-LTP will decrease with age, and the decrease will be more pronounced in healthy controls than in patients.
- Conditions
- Schizophrenia
- Being tested
- Brain Stimulation via Transcranial Magnetic Stimulation
- Keywords
- Transcranial Magnetic Stimulation (TMS), Dorsolateral Prefrontal Cortex (DLPFC), Schizophrenia, Working Memory, Paired Associative Stimulation (PAS), Electroencephalography (EEG), Cognition
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brain Stimulation via Transcranial Magnetic StimulationOther
PAS-25 will consist of 180 PNS delivered to right median nerve, each paired with a single TMS pulse delivered over left DLPFC with an interstimulus interval of 25 ms. This ISI was designed to generate approximately synchronous arrival of both inputs in M1 and was reported to markedly enhance TMS-induced MEP following PAS-25.
Patients with schizophrenia will be asked to continue with a 2-week course (5 days/week) of daily PAS-25 or PAS-100 to assess potential of a repetitive course of PAS-25 on enhancing working memory in patients with Schizophrenia. One and seven days after the 2-week course PAS-25 or PAS-100, patients with schizophrenia will be assessed with the N-back task.
| Study group | Role | What they receive |
|---|---|---|
| PAS 25 | Active comparator | In humans, paired associative stimulation (PAS-25) is a transcranial magnetic stimulation (TMS) protocol that has been shown to result in LTP-like plasticity (PAS-LTP) in the motor cortex (M1). PAS-LTP has been shown to be dependent on the NMDAR and to correlate significantly with performance on a motor learning task. Receives: Other: Brain Stimulation via Transcranial Magnetic Stimulation |
| PAS 100 | Sham comparator | To control for non-specific effects of PAS protocol, the investigators will use a modified PAS protocol (PAS-100) that does not result in any neurophysiologic effects. Patients with schizophrenia and healthy controls will be assessed first with the N-back task and then randomized Receives: Other: Brain Stimulation via Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in working memory
The N-Back is a working memory task where the subject is presented with a sequence of stimuli (letters). The task consists of indicating when the current stimulus matches the one from n steps earlier in the sequence. The load factor n can be adjusted to make the task more or less difficult. Subjects are required to complete the 0, 1, 2 and 3 back at baseline, 1 day post PAS delivery and 7 days post PAS.
Measured: 1 day and 7 days post N-back task
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), National Alliance for Research on Schizophrenia and Depression
- Responsible party
- Principal investigator, Tarek Rajji, Centre for Addiction and Mental Health
- Investigators
- Tarek K Rajji, MD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01545999
- Sponsor's protocol ID
- #165/2009-04
- Status last verified
- Apr 2026
- First submitted
- 17 Jan 2012
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paired Associative Stimulation in the Dorsolateral Prefrontal Cortex in Patients With Schizophrenia: a Combined Transcranial Magnetic Stimulation and Electroencephalography Study Across the Life Span
- ClinicalTrials.gov ID
- NCT01545999
- Acronym / sponsor ID
- #165/2009-04
- Conditions
- Schizophrenia
- Keywords
- Transcranial Magnetic Stimulation (TMS), Dorsolateral Prefrontal Cortex (DLPFC), Schizophrenia, Working Memory, Paired Associative Stimulation (PAS), Electroencephalography (EEG), Cognition
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), National Alliance for Research on Schizophrenia and Depression
- Study start
- Mar 2012 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 7 Mar 2012 (estimated)
- 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.
The purpose of this study is to
- assess the effect of PAS in schizophrenia in the dorsolateral prefrontal cortex (DLPFC)
- assess the effect of PAS induced long-term potentiation (LTP) on the performance of patients with schizophrenia on a cognitive task related to DLFPC.
Detailed description
Neuroplasticity refers to changes in the strength of communication between different neurons. Long-term potentiation (LTP) is one form of neuroplasticity and refers to the strengthening of such communication. LTP is believed to be a cellular substrate of learning and memory. Paired associative stimulation (PAS) is a transcranial magnetic stimulation (TMS) paradigm that is believed to induce LTP in human subjects. However, its effects have been shown to be minimal in patients with schizophrenia suggesting impaired LTP in schizophrenia. The lack of PAS effect in schizophrenia has been observed in the motor cortex (M1). Thus, the investigators propose to assess the effect of PAS in schizophrenia in the dorsolateral prefrontal cortex (DLPFC), an area of the brain that is especially relevant to learning and memory, and to the pathology in schizophrenia. The investigators also propose to assess the effect of PAS induced LTP on the performance of patients with schizophrenia on a cognitive task that is related to DLFPC.
Hypothesis 1: Patients with schizophrenia will have reduced PAS-LTP in DLPFC in comparison with healthy controls.
Hypothesis 2a: PAS-LTP in patients with schizophrenia and healthy controls randomized to PAS-25 and PAS-100 will correlate with performance on the N-back task at baseline (pre-PAS).
Hypothesis 2b: Healthy controls randomized to PAS-25 will perform better after one session of PAS-25 on the 1- and 7-day N-back task compared to healthy controls randomized to PAS-100.
Hypothesis 2c: Among healthy controls randomized to PAS-25, the magnitude of improvement on the 1- and 7-day N-back task (compared to pre-PAS) that is in excess of the magnitude of improvement on the 1- and 7-day N-back task among subjects randomized to PAS-100 will correlate with the degree of PAS-LTP.
Hypothesis 3a: Patients with schizophrenia who are randomized to receive a 2-week course of PAS-25 will have improved PAS-LTP in DLPFC compared to patients with schizophrenia randomized to 2-week course of PAS-100.
Hypothesis 3b: Patients with schizophrenia who are randomized to receive a 2-week course of PAS-25 will have improved performance on the N-back working memory task compared to patients with schizophrenia randomized to 2-week PAS-100 at 1- and 7-day post-PAS course N-back.
Hypothesis 3c: Patients with schizophrenia who are randomized to receive a 2-week course of PAS-25 will have increased DLPFC cortical thickness compared to patients with schizophrenia randomized to 2-week PAS-100.
Hypothesis 4: Among patients with schizophrenia and healthy controls, PAS-LTP will decrease with age, and the decrease will be more pronounced in healthy controls than in patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PAS 25 | Active comparator | Other: Brain Stimulation via Transcranial Magnetic StimulationIn humans, paired associative stimulation (PAS-25) is a transcranial magnetic stimulation (TMS) protocol that has been shown to result in LTP-like plasticity (PAS-LTP) in the motor cortex (M1). PAS-LTP has been shown to be dependent on the NMDAR and to correlate significantly with performance on a motor learning task. |
| PAS 100 | Sham comparator | Other: Brain Stimulation via Transcranial Magnetic StimulationTo control for non-specific effects of PAS protocol, the investigators will use a modified PAS protocol (PAS-100) that does not result in any neurophysiologic effects. Patients with schizophrenia and healthy controls will be assessed first with the N-back task and then randomized |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Age 18 or above
- All races and ethnicities.
- Females and males.
- Meet DSM-IV TR criteria for a current diagnosis of schizophrenia or schizoaffective disorder.
- Clinically stable as operationalized by (1) either having not been hospitalized within 3 months or having been hospitalized for 3 months or more prior to assessment, and (2) having had no change in antipsychotic medication dosage within the 4 weeks prior to assessment.
Key exclusion criteria (12 listed)
- Meets criteria for a cognitive disorder secondary to a neurological or other medical disorder affecting the central nervous system (for example, multiple sclerosis, history of traumatic brain injury, stroke, untreated hypothyroidism).
- Mini Mental Status Examination score of 17 and less because a subject with a very low MMSE score is unlikely to be able to compete the NP battery.
- Diagnosis of bipolar disorder or current major depressive episode.
- Meets diagnostic criteria for current alcohol or other drug dependence within 6 months of testing
- Electroconvulsive Therapy (ECT) within 6 months of testing.
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 |
|---|---|---|
| Brain Stimulation via Transcranial Magnetic StimulationPAS-25 will consist of 180 PNS delivered to right median nerve, each paired with a single TMS pulse delivered over left DLPFC with an interstimulus interval of 25 ms. This ISI was designed to generate approximately synchronous arrival of both inputs in M1 and was reported to markedly enhance TMS-induced MEP following PAS-25. Patients with schizophrenia will be asked to continue with a 2-week course (5 days/week) of daily PAS-25 or PAS-100 to assess potential of a repetitive course of PAS-25 on enhancing working memory in patients with Schizophrenia. One and seven days after the 2-week course PAS-25 or PAS-100, patients with schizophrenia will be assessed with the N-back task. | Other | PAS 100, PAS 25 |
Primary outcome
Changes in working memory
Time frame: 1 day and 7 days post N-back task
The N-Back is a working memory task where the subject is presented with a sequence of stimuli (letters). The task consists of indicating when the current stimulus matches the one from n steps earlier in the sequence. The load factor n can be adjusted to make the task more or less difficult. Subjects are required to complete the 0, 1, 2 and 3 back at baseline, 1 day post PAS delivery and 7 days post PAS.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
- Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teachingLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Tarek K Rajji, MD principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Brain Stimulation via Transcranial Magnetic Stimulation in people with Schizophrenia, run by Centre for Addiction and Mental Health at 1 site in Canada.
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 12 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
This study is still under way. Results are not available in the source record yet.
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?
Changes in working memory (time frame: 1 day and 7 days post N-back task). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Apr 2026.