Schizophrenia
Conditions
Keywords
Schizoaffective disorder, Auditory Hallucinations, Voices, Repetitive Transcranial Magnetic Stimulation, rTMS, Wernicke's Area, Middle Temporal Cortex, Persistent Auditory Hallucinations, Previously Participated in Parent rTMS Protocol
Brief summary
The primary purpose of this study was to conduct fMRI neuroimaging studies prior to and subsequent to the rTMS intervention. The intent was to ascertain changes in regional brain activation and connectivity that most robustly predict level of improvement in auditory hallucinations elicited by bilateral rTMS as assessed by the primary outcome variables.
Detailed description
This study is an extension of previous clinical trials (NCT00308997 and NCT00567281) that were initiated in 2006. This study record provides the results for the amended study NCT00567281 (originally called a 'third arm') that was discontinued following the passing of Dr. Ralph Hoffman. The primary purpose of the study was to conduct fMRI neuroimaging studies prior to and subsequent to the rTMS intervention. The intent was to ascertain changes in regional brain activation and connectivity that most robustly predict level of improvement in auditory hallucinations elicited by bilateral rTMS as assessed by our primary outcome variables. It was hoped that this combined fMRI/rTMS study would provide critical new insights into the neurobiological basis of auditory hallucinations. The results presented are what was summarized following Dr. Hoffman's passing and were compiled by Dr. Philip Corlett.
Interventions
Week 1 treatment includes rTMS for 5 sessions to both the left and right Wernicke's area (BA22) synchronous with rTMS to opposite hemisphere middle temporal cortex (BA21). Week 2 treatment includes rTMS given for 5 sessions with positions reversed (e.g., if Wernicke's stimulation was on the left during Week 1, position of rTMS will switch to the right side during Week 2 and vice-versa). As in Week 1, active rTMS will also be given synchronously to the opposite hemisphere middle temporal cortex. Weeks 3 and 4 include 10 stimulation sessions to the configuration of sites producing greater improvement in comparing results of Week 1 and Week 2. rTMS for each stimulation session will be given at 1-Hertz (once per second) for 16 minutes without interruption.
Sponsors
National Institute of Mental Health (NIMH)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Previously enrolled in our parent rTMS trial with passage of at least six months since last received active rTMS
Exclusion criteria
* Active substance abuse or alcohol abuse * Pregnancy * Dose or type of psychiatric medication changed within the 4 weeks prior to study entry * Recent head trauma, seizures, or significant unstable medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PANSS Composite Positive Symptoms Hallucination Score | baseline to 4 weeks | The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS positive symptoms hallucinication score has a range of 1-7. Higher scores indicate more severe positive symptoms in patients with schizophrenia. |
| PANSS Composite Negative Symptom Scale | baseline to 4 weeks | The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS negative scale has 7 Items, with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe negative symptoms in patients with schizophrenia. |
| PANSS Total Score | baseline to 4 weeks | The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS total score has a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms in patients with schizophrenia. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Non-randomized Bilateral rTMS Active bilateral rTMS to left/right Wernicke's area and opposite side middle temporal gyrus
Magstim Rapid 2 system triggering Magstim Super Rapid system: Week 1 treatment includes rTMS for 5 sessions to both the left and right Wernicke's area (BA22) synchronous with rTMS to opposite hemisphere middle temporal cortex (BA21). Week 2 treatment includes rTMS given for 5 sessions with positions reversed (e.g., if Wernicke's stimulation was on the left during Week 1, position of rTMS will switch to the right side during Week 2 and vice-versa). As in Week 1, active rTMS will also be given synchronously to the opposite hemisphere middle temporal cortex. Weeks 3 and 4 include 10 stimulation sessions to the configuration of sites producing greater improvement in comparing results of Week 1 and Week 2. rTMS for each stimulation session will be given at 1-Hertz (once per second) for 16 minutes without interruption. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Non-randomized Bilateral rTMS | — |
|---|---|---|
| Age, Continuous | 31 years STANDARD_DEVIATION 10 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 15 participants | — |
| Sex: Female, Male Female | 7 Participants | — |
| Sex: Female, Male Male | 8 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
PANSS Composite Negative Symptom Scale
The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS negative scale has 7 Items, with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe negative symptoms in patients with schizophrenia.
Time frame: baseline to 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-randomized Bilateral rTMS | PANSS Composite Negative Symptom Scale | Baseline | 16.9 units on a scale | Standard Deviation 5.22 |
| Non-randomized Bilateral rTMS | PANSS Composite Negative Symptom Scale | 4 weeks | 12.53 units on a scale | Standard Deviation 4.54 |
p-value: 0.004t-test, 2 sided
Primary
PANSS Composite Positive Symptoms Hallucination Score
The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS positive symptoms hallucinication score has a range of 1-7. Higher scores indicate more severe positive symptoms in patients with schizophrenia.
Time frame: baseline to 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-randomized Bilateral rTMS | PANSS Composite Positive Symptoms Hallucination Score | Baseline | 5.19 units on a scale | Standard Deviation 0.85 |
| Non-randomized Bilateral rTMS | PANSS Composite Positive Symptoms Hallucination Score | 4 weeks | 4.19 units on a scale | Standard Deviation 1.07 |
p-value: 0.01t-test, 2 sided
Primary
PANSS Total Score
The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS total score has a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms in patients with schizophrenia.
Time frame: baseline to 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-randomized Bilateral rTMS | PANSS Total Score | 4 weeks | 53.2 units on a scale | Standard Deviation 14.9 |
| Non-randomized Bilateral rTMS | PANSS Total Score | Baseline | 67.8 units on a scale | Standard Deviation 17.9 |
p-value: 0.001t-test, 2 sided