Treatment of Negative Symptoms of Schizophrenia With Tran... | NCT00517075

Name	Class
National Institute of Mental Health (NIMH)	NIH
National Alliance for Research on Schizophrenia and Depression	OTHER

Description Module

Detailed Description

Most treatments for schizophrenia are helpful in treating positive symptoms (e.g. hallucinations), whereas negative symptoms (e.g. low social drive) are only partially responsive to medication. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive way of stimulating the brain that has been FDA approved for the treatment of depression and has shown promise in schizophrenia.

In rTMS therapy, a device called a "magnetic stimulator" provides electrical energy to a magnetic coil that delivers a magnetic field. When the coil is placed against the surface of the head, the magnetic field can cause parts of the brain to either increase or decrease in activity, depending on how quickly the magnetic pulses are delivered. This study is designed to test whether high-frequency rTMS delivered to an area near the front of the head, called the dorsolateral prefrontal cortex, can improve the "negative symptoms" of schizophrenia, which include decreased thinking, difficulty motivating, and social withdrawal.

Participation in the first phase of the study consists of sessions lasting about 45 minutes per day, 5 days a week, for 4 weeks. Twenty-four subjects will be randomly assigned to receive four weeks of either active (real) rTMS or inactive (sham) rTMS. Patients will receive magnetic resonance imaging (MRI) of their brains to help locate where the rTMS should be applied. Symptoms will be rated at baseline, during the rTMS course, and at the end of the 4 weeks. Patients who do not meet response criteria after the four weeks of the randomized phase will be offered active (real) daily rTMS for an additional four weeks in the open phase of the study. All patients will have two monthly repeat assessments after their last rTMS session to examine the persistence of benefit.

We will also collect measures of motor cortex excitability (performed with single pulse TMS) at baseline, at the end of the randomized and, if applicable, the open study phase, and at each of the two follow-up assessments to determine whether changes in these measures correlate with clinical improvement.

In addition, we will look at brain dynamics using electroencephalography (EEG) pre- and post-rTMS in the first and last sessions of each study phase. We will also assess the effects of rTMS on cigarette use, as schizophrenia patients are known to have increased prevalence of nicotine dependence. There is also preliminary evidence that high frequency rTMS to the left DLPFC decreases cigarette smoking.

Label	Type	Description	Intervention Names
A	Experimental	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind	Device: Transcranial Magnetic Stimulation (TMS)
B	Active Comparator	Active high frequency rTMS to the left dorsolateral prefrontal cortex	Device: Transcranial Magnetic Stimulation (TMS)
C	Sham Comparator	Sham (placebo) high frequency rTMS to the left dorsolateral prefrontal cortex or left infero-parietal lobe, active/sham condition randomized (2:1), double-blind	Device: Transcranial Magnetic Stimulation (TMS)
Open cross over high frequency rTMS	Experimental	Following the randomization phase with three arms, subjects who did not respond, have the possibility of receiving open active treatment to the target that they did not receive treatment to in the randomization phase. (i.e. randomized to IPL --> open phase DLPFC and vice versa)	Device: repetitive transcranial magnetic stimulation

Name	Type	Description	Arm Group Labels	Other Names
Transcranial Magnetic Stimulation (TMS)	Device	For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

Measure	Description	Time Frame
Clinical Improvement of Negative Symptoms (Positive and Negative Syndrome Scale [PANSS] Negative Symptoms Subscale) Relative to Pre-treatment Baseline.		At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.

Measure	Description	Time Frame
Global Clinical Improvement		At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.
Social Functioning		At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female inpatients or outpatients, 18 to 55 years of age.
Primary diagnosis by DSM-IV criteria for Schizophrenia or Schizoaffective Disorder.
Capacity and willingness to give informed consent.
Engaged in ongoing treatment with a psychiatrist.
PANSS negative symptoms subscale score of ≥ 15.
English speaking.
Patients must have stable symptoms as defined by not requiring a change in antipsychotic medication for at least 4 weeks or at least 2 weeks for other psychotropic agents (e.g. antidepressants) prior to entering the study. Patients will not be included in the study if the research team thinks that modifications could be made to maximize their medication regimen at initial evaluation.
Able to adhere to the treatment schedule.
Able to commute to NYC for daily treatments (Monday - Friday) for at least 4 weeks.

Exclusion Criteria:

Individuals diagnosed by the investigator with the following conditions (current unless otherwise stated): Current affective disorder including Major Depressive Disorder, Bipolar Affective Disorder; substance abuse or dependence within the past year (except nicotine and caffeine).
An Axis II Personality Disorder, which in the judgment of the investigator may hinder the patient in completing the procedures required by the study protocol.

Other exclusion criteria include those common to every TMS protocol:

Individuals with a clinically defined neurological disorder or insult including, but not limited to: Any condition likely to be associated with increased intracranial pressure; Space occupying brain lesion; Any history of seizure EXCEPT those therapeutically induced by ECT; History of cerebrovascular accident; Transient ischemic attack within two years; Cerebral aneurysm; Dementia; Parkinson's disease; Huntington's chorea; or Multiple sclerosis.
Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), history of epilepsy or seizure in first-degree relatives, having metal inside the head, or history of significant head trauma with loss of consciousness for 5 minutes.
Prior adverse reaction to TMS.
History of treatment with rTMS therapy for any disorder.
Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease.
Intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed.
Current illicit drug use.
Clinically significant laboratory abnormality, in the opinion of the investigator. (Note: Clinically significant laboratory abnormality refers to patient lab results that fall outside the established normal ranges, may be indicative of the presence of a medical condition, and are not thought to reflect an artifact or routine lab error (e.g. hemolysis). Results of laboratory tests are reviewed by the study physician prior to any treatment. Abnormal lab results of clinical significance that cannot be resolved (e.g. by repeating the test to rule out laboratory error or poor quality of the original sample) will lead to exclusion from the study.)
Known or suspected pregnancy.
Women who are breast-feeding.
Women of child-bearing potential not using a medically accepted form of contraception when engaging in sexual intercourse.
Wearing medicinal skin patches during the MRI scan.

Name	Affiliation	Role
Arielle D. Stanford, MD	New York State Psychiatric Institute / Columbia University College of Physicians and Surgeons	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
New York State Psychiatric Institute		New York	New York	10032	United States

PubMed Identifier	Type	Citation	Retractions
15697042	Background	Hajak G, Marienhagen J, Langguth B, Werner S, Binder H, Eichhammer P. High-frequency repetitive transcranial magnetic stimulation in schizophrenia: a combined treatment and neuroimaging study. Psychol Med. 2004 Oct;34(7):1157-63. doi: 10.1017/s0033291704002338.
15896231	Background	Sachdev P, Loo C, Mitchell P, Malhi G. Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: a pilot investigation. Psychiatry Clin Neurosci. 2005 Jun;59(3):354-7. doi: 10.1111/j.1440-1819.2005.01382.x.

Label	URL
Division of Brain Stimulation and Therapeutic Modulation, Columbia University	View source

ID	Title	Description
FG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

Arm/Group Information

ID	Title	Description
BG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
BG001	Active High Frequency rTMS	Active high frequency rTMS to the left dorsolateral prefrontal cortex Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
BG002	Sham/Placebo	Sham (placebo) high frequency rTMS to the left dorsolateral prefrontal cortex or left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
BG003	Open Cross Over High Frequency rTMS	Following the randomization phase with three arms, subjects who did not respond, have the possibility of receiving open active treatment to the target that they did not receive treatment to in the randomization phase. (i.e. randomized to IPL --> open phase DLPFC and vice versa) repetitive transcranial magnetic stimulation: For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG0000 BG0010 BG0020 BG0030 BG0040

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

Clinical Improvement of Negative Symptoms (Positive and Negative Syndrome Scale [PANSS] Negative Symptoms Subscale) Relative to Pre-treatment Baseline.

P.I. has left the institution and NYSPI has no access to the data. Results will not be analyzed or presented.

Posted

At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.

ID	Title	Description
OG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
OG001	Active High Frequency rTMS	Active high frequency rTMS to the left dorsolateral prefrontal cortex Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
OG002	Sham/Placebo	Sham (placebo) high frequency rTMS to the left dorsolateral prefrontal cortex or left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
OG003	Open Cross Over High Frequency rTMS	Following the randomization phase with three arms, subjects who did not respond, have the possibility of receiving open active treatment to the target that they did not receive treatment to in the randomization phase. (i.e. randomized to IPL --> open phase DLPFC and vice versa) repetitive transcranial magnetic stimulation: For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Global Clinical Improvement

P.I. has left the institution and NYSPI has no access to the data. Results will not be analyzed or presented.

Posted

At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.

ID	Title	Description
OG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
OG001	Active High Frequency rTMS	Active high frequency rTMS to the left dorsolateral prefrontal cortex Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

Secondary

Social Functioning

P.I. has left the institution and NYSPI has no access to the data. Results will not be analyzed or presented.

Posted

At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.

ID	Title	Description
OG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
OG001	Active High Frequency rTMS	Active high frequency rTMS to the left dorsolateral prefrontal cortex Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

Secondary

Depression

P.I. has left the institution and NYSPI has no access to the data. Results will not be analyzed or presented.

Posted

At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.

ID	Title	Description
OG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
OG001	Active High Frequency rTMS	Active high frequency rTMS to the left dorsolateral prefrontal cortex Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

Secondary

Theory of Mind

P.I. has left the institution and NYSPI has no access to the data. Results will not be analyzed or presented.

Posted

At baseline and the end of each study phase (random and open)

ID	Title	Description
OG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
OG001	Active High Frequency rTMS	Active high frequency rTMS to the left dorsolateral prefrontal cortex Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

Secondary

Smoking Behaviors

P.I. has left the institution and NYSPI has no access to the data. Results will not be analyzed or presented.

Posted

At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.

ID	Title	Description
OG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
OG001	Active High Frequency rTMS	Active high frequency rTMS to the left dorsolateral prefrontal cortex Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

Secondary

Cognitive Function

P.I. has left the institution and NYSPI has no access to the data. Results will not be analyzed or presented.

Posted

At baseline, the first and last rTMS sessions of each study phase (random and open), and at monthly follow-up visits.

ID	Title	Description
OG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
OG001	Active High Frequency rTMS	Active high frequency rTMS to the left dorsolateral prefrontal cortex Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

Secondary

Cortical Excitability

P.I. has left the institution and NYSPI has no access to the data. Results will not be analyzed or presented.

Posted

At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.

ID	Title	Description
OG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
OG001	Active High Frequency rTMS	Active high frequency rTMS to the left dorsolateral prefrontal cortex Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

Arm/Groups

ID	Title	Description
EG000	High Frequency rTMS	high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
EG001	Active High Frequency rTMS	Active high frequency rTMS to the left dorsolateral prefrontal cortex Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
EG002	Sham/Placebo	Sham (placebo) high frequency rTMS to the left dorsolateral prefrontal cortex or left infero-parietal lobe, active/sham condition randomized (2:1), double-blind Transcranial Magnetic Stimulation (TMS): For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.
EG003	Open Cross Over High Frequency rTMS	Following the randomization phase with three arms, subjects who did not respond, have the possibility of receiving open active treatment to the target that they did not receive treatment to in the randomization phase. (i.e. randomized to IPL --> open phase DLPFC and vice versa) repetitive transcranial magnetic stimulation: For rTMS, the coil is held flat on the scalp. 40 trains of 10 Hz rTMS will be delivered in trains lasting 4 seconds, with an intertrain interval of 26 seconds, for a total of 20 minutes (1600 pulses per day) at 100% motor threshold. Subjects will receive rTMS once a day, 5 days a week, for 4 weeks. During the first week of rTMS sessions only, in the event that the patient cannot tolerate these stimulation parameters, intensity relative to motor threshold may be titrated downward, in a masked fashion, to 80%, with all other dose parameters remaining the same.

ID	Term
D012559	Schizophrenia
D011618	Psychotic Disorders

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001523	Mental Disorders

ID	Term
D055909	Magnetic Field Therapy
D013812	Therapeutics