search
Back to results

Treatment of Negative Symptoms of Schizophrenia With Transcranial Magnetic Stimulation (TMS)

Primary Purpose

Schizophrenia, Schizoaffective Disorder

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Transcranial Magnetic Stimulation (TMS)
Transcranial Magnetic Stimulation (TMS)
Transcranial Magnetic Stimulation (TMS)
repetitive transcranial magnetic stimulation
Sponsored by
New York State Psychiatric Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Transcranial Magnetic Stimulation, Repetitive Transcranial Magnetic Stimulation, Schizophrenia, Schizoaffective Disorder, Treatment, Negative Symptoms, Social Dysfunction, TMS, rTMS

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • New York State Psychiatric Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Sham Comparator

Experimental

Arm Label

A

B

C

Open cross over high frequency rTMS

Arm Description

high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind

Active high frequency rTMS to the left dorsolateral prefrontal cortex

Sham (placebo) high frequency rTMS to the left dorsolateral prefrontal cortex or left infero-parietal lobe, active/sham condition randomized (2:1), double-blind

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)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Global Clinical Improvement
Social Functioning
Depression
Theory of Mind
Smoking Behaviors
Cognitive Function
Cortical Excitability

Full Information

First Posted
August 14, 2007
Last Updated
January 12, 2017
Sponsor
New York State Psychiatric Institute
Collaborators
National Institute of Mental Health (NIMH), National Alliance for Research on Schizophrenia and Depression
search

1. Study Identification

Unique Protocol Identification Number
NCT00517075
Brief Title
Treatment of Negative Symptoms of Schizophrenia With Transcranial Magnetic Stimulation (TMS)
Official Title
Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Negative Symptoms and Social Dysfunction in Schizophrenia Patients
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Terminated
Why Stopped
Unable to adequately recruit subjects.
Study Start Date
September 2004 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New York State Psychiatric Institute
Collaborators
National Institute of Mental Health (NIMH), National Alliance for Research on Schizophrenia and Depression

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will test whether repetitive transcranial magnetic stimulation (rTMS) is helpful in treating negative symptoms and social deficits of schizophrenia. This will be the first rTMS study to assess social function and social cognition. Hypoactivity in the dorsolateral prefrontal cortex (DLPFC) has been implicated in generating the negative symptoms of schizophrenia. Abnormalities in the left inferior parietal lobe (IPL) have also been associated with negative symptoms. We hypothesize that high frequency rTMS applied to the hypoactive left DLPFC or to the left IPL in individuals with schizophrenia will reduce negative symptom severity more than sham (placebo) rTMS as assessed by the Positive and Negative Syndrome Scale (PANSS) negative symptoms subscale. We hypothesize that high frequency rTMS applied to the left DLPFC or to the left IPL in schizophrenia patients will improve social dysfunction more than sham (placebo) rTMS as assessed by the Social Adjustment Scale, the Social Adaptation Self-Evaluation Scale and the Social Functioning Scale.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder
Keywords
Transcranial Magnetic Stimulation, Repetitive Transcranial Magnetic Stimulation, Schizophrenia, Schizoaffective Disorder, Treatment, Negative Symptoms, Social Dysfunction, TMS, rTMS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
high frequency rTMS to the left infero-parietal lobe, active/sham condition randomized (2:1), double-blind
Arm Title
B
Arm Type
Active Comparator
Arm Description
Active high frequency rTMS to the left dorsolateral prefrontal cortex
Arm Title
C
Arm Type
Sham Comparator
Arm Description
Sham (placebo) high frequency rTMS to the left dorsolateral prefrontal cortex or left infero-parietal lobe, active/sham condition randomized (2:1), double-blind
Arm Title
Open cross over high frequency rTMS
Arm Type
Experimental
Arm Description
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)
Intervention Type
Device
Intervention Name(s)
Transcranial Magnetic Stimulation (TMS)
Other Intervention Name(s)
Magstim Rapid 2
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Transcranial Magnetic Stimulation (TMS)
Other Intervention Name(s)
Magstim Rapid 2
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Transcranial Magnetic Stimulation (TMS)
Other Intervention Name(s)
Magstim Rapid 2
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
repetitive transcranial magnetic stimulation
Other Intervention Name(s)
MagStim Rapid2
Intervention Description
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.
Primary Outcome Measure Information:
Title
Clinical Improvement of Negative Symptoms (Positive and Negative Syndrome Scale [PANSS] Negative Symptoms Subscale) Relative to Pre-treatment Baseline.
Time Frame
At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.
Secondary Outcome Measure Information:
Title
Global Clinical Improvement
Time Frame
At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.
Title
Social Functioning
Time Frame
At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.
Title
Depression
Time Frame
At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.
Title
Theory of Mind
Time Frame
At baseline and the end of each study phase (random and open)
Title
Smoking Behaviors
Time Frame
At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.
Title
Cognitive Function
Time Frame
At baseline, the first and last rTMS sessions of each study phase (random and open), and at monthly follow-up visits.
Title
Cortical Excitability
Time Frame
At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arielle D. Stanford, MD
Organizational Affiliation
New York State Psychiatric Institute / Columbia University College of Physicians and Surgeons
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York State Psychiatric Institute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15697042
Citation
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.
Results Reference
background
PubMed Identifier
15896231
Citation
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.
Results Reference
background
PubMed Identifier
16254067
Citation
Jin Y, Potkin SG, Kemp AS, Huerta ST, Alva G, Thai TM, Carreon D, Bunney WE Jr. Therapeutic effects of individualized alpha frequency transcranial magnetic stimulation (alphaTMS) on the negative symptoms of schizophrenia. Schizophr Bull. 2006 Jul;32(3):556-61. doi: 10.1093/schbul/sbj020. Epub 2005 Oct 27.
Results Reference
background
Links:
URL
http://www.brainstimulation.columbia.edu/
Description
Division of Brain Stimulation and Therapeutic Modulation, Columbia University
URL
http://columbiapsychiatry.org/
Description
Department of Psychiatry, Columbia University
URL
http://www.nyspi.org/
Description
New York State Psychiatric Institute

Learn more about this trial

Treatment of Negative Symptoms of Schizophrenia With Transcranial Magnetic Stimulation (TMS)

We'll reach out to this number within 24 hrs