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Patients with schizophrenia spectrum disorder (SSD) will be exposed to active and sham repetitive transcranial magnetic stimulation (rTMS) in separate sessions. SSD-related biomarkers will be assessed before and after the rTMS administration.
Electrical neural oscillations of the brain can be measured at many levels, ranging from single cell to local field potentials in animals, to large-scale synchronized activities in the human scalp. New evidence suggests that there may be common underlying abnormalities in oscillatory activities that are associated with schizophrenia-related cognitive and functional impairments. There is currently no treatment for these electrical oscillation dysfunctions. Transcranial magnetic stimulation (TMS) provides a non-invasive means for altering brain electrical neural activity. TMS has been approved by FDA for the treatment of depression and many other mental disorders. It has been used in a wide range of clinical research, especially in neurology and psychiatry. The investigators aim to develop TMS paradigms that will modulate brain responses during basic sensory to more complex cognitive performance and determine the parameters in anatomic locations and TMS modalities that may effectively and safely modulate neural activities. If the current experiments successfully identified TMS methods/paradigms that improve neural oscillation and cognitive performances in schizophrenia patients, in the future (not part of the current protocol), the investigators can then develop specific TMS treatment that may correct abnormal brain function and improve cognition and clinical symptoms of schizophrenia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active rTMS first and sham rTMS second | Other | Participants in this arm will receive active rTMS in one visit first, then receive sham rTMS in another visit. |
|
| Sham rTMS first and active rTMS second | Other | Participants in this arm will receive sham rTMS in one visit first, then receive active rTMS in another visit. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| active rTMS first, then sham rTMS | Device | Active rTMS is delivered on the first visit, then sham rTMS is delivered on the second visit. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change of Resting-state Functional Connectivity (rsFC) by Active and Sham rTMS | The strength of rsFC was first defined by correlation coefficient (r). Because the distribution of r values is highly skewed, z scores (normally distributed) were computed via fisher r-to-z transform. The z score central value (i.e., z score of 0) represents no relationship between the two brain regions. A positive (negative) z score indicates a positive (negative) association between the two brain regions. Stronger rsFC (i.e., larger positive z score) was related to stronger connection between the two brain regions. The differences of rsFC between active and sham were reported. A positive (negative) value of rsFC change suggests the rsFC was enhanced (weakened) by active TMS. | 2 weeks |
| Change of Mismatch Negativity (MMN) From Electroencephalography (EEG) Signals by Active and Sham rTMS | TMS effect is explored by comparing MMN changes from active and sham rTMS. MMN is measured by subtracting the averaged EEG response to a set of standard stimuli from the averaged response to rarer deviant stimuli, and taking the amplitude of this difference wave in a given time window. The differences of MMN between active and sham were reported. A negative (positive) value of rsFC change suggests the MMN was enhanced (weakened) by active TMS. | 2 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xiaoming Du, PhD | University of Maryland, Baltimore | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland, Baltimore | Baltimore | Maryland | 21228 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Active rTMS First and Sham rTMS Second | Participants in this arm will receive active rTMS in one visit first, then receive sham rTMS in another visit. active rTMS first, then sham rTMS: Active rTMS is delivered on the first visit, then sham rTMS is delivered on the second visit. |
| FG001 | Sham rTMS First and Active rTMS Second | Participants in this arm will receive sham rTMS in one visit first, then receive active rTMS in another visit. sham rTMS first, then active rTMS: Sham rTMS is delivered on the first visit, then active rTMS is delivered on the second visit. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Active rTMS First and Sham rTMS Second | Participants in this arm will receive active rTMS in one visit first, then receive sham rTMS in another visit. active rTMS first, then sham rTMS: Active rTMS is delivered on the first visit, then sham rTMS is delivered on the second visit. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change of Resting-state Functional Connectivity (rsFC) by Active and Sham rTMS | The strength of rsFC was first defined by correlation coefficient (r). Because the distribution of r values is highly skewed, z scores (normally distributed) were computed via fisher r-to-z transform. The z score central value (i.e., z score of 0) represents no relationship between the two brain regions. A positive (negative) z score indicates a positive (negative) association between the two brain regions. Stronger rsFC (i.e., larger positive z score) was related to stronger connection between the two brain regions. The differences of rsFC between active and sham were reported. A positive (negative) value of rsFC change suggests the rsFC was enhanced (weakened) by active TMS. | Posted | Mean | Standard Error | z score of functional connectivity | 2 weeks |
|
From baseline to the time when the participant completes or quits the study (up to 1 month).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active rTMS | Participants who received active rTMS in either the first or the second visit. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Xiaoming Du | UTHealth Houston | 4438829717 | Xiaoming.Du@uth.tmc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 18, 2023 | Nov 5, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 6, 2023 | Dec 16, 2025 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D011618 | Psychotic Disorders |
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| sham rTMS first, then active rTMS | Device | Sham rTMS is delivered on the first visit, then active rTMS is delivered on the second visit. |
|
| Sham rTMS First and Active rTMS Second |
Participants in this arm will receive sham rTMS in one visit first, then receive active rTMS in another visit. sham rTMS first, then active rTMS: Sham rTMS is delivered on the first visit, then active rTMS is delivered on the second visit. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Sham rTMS | Participants who received sham rTMS in either the first or second visit. |
|
|
| Primary | Change of Mismatch Negativity (MMN) From Electroencephalography (EEG) Signals by Active and Sham rTMS | TMS effect is explored by comparing MMN changes from active and sham rTMS. MMN is measured by subtracting the averaged EEG response to a set of standard stimuli from the averaged response to rarer deviant stimuli, and taking the amplitude of this difference wave in a given time window. The differences of MMN between active and sham were reported. A negative (positive) value of rsFC change suggests the MMN was enhanced (weakened) by active TMS. | Posted | Mean | Standard Error | microvolts | 2 weeks |
|
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| 0 |
| 10 |
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Sham rTMS | Participants who received sham rTMS in either the first or the second visit. | 0 | 10 | 0 | 10 | 0 | 10 |
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