Schizophrenia
Conditions
Brief summary
The primary aim of this protocol is to determine whether the use of repetitive transcranial magnetic stimulation (rTMS) over vermis of the cerebellum may be safe and therapeutically effective in patients with schizophrenia. Because this is the first evaluation of this treatment in this population, the focus of this study is safety.
Interventions
DEVICETranscranial magnetic stimulation via MagPro x100 device
Participants will receive 10 repetitive transcranial magnetic stimulation sessions to the vermis of cerebellum using the MagPro x100 TMS device. These 10 rTMS sessions will be administered from Monday to Friday in five days, twice a day with a minimum of 4-hour gap between the sessions. Repetitive TMS will be applied with the intermittent theta burst pattern (iTBS). These parameters are known to cause excitation in brain activity. Anatomically precise localization of rTMS will be achieved using a frameless stereotactic system.
Sponsors
Beth Israel Deaconess Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age between 18-65 years 2. Diagnosis of schizophrenia according to DSM-IV criteria(by a board-certified psychiatrist)
Exclusion criteria
1. Prior neurosurgical procedures 2. Any history of seizure 3. Previous head injury 4. Contraindication to TMS: 1. Implanted pacemaker 2. Medication pump 3. Vagal stimulator 4. Deep brain stimulator 5. Metallic hardware in the head or scalp: shrapnel, surgical clips, or fragments from welding 6. Signs of increased intracranial pressure 5. TENS unit and ventriculo-peritoneal shunt 6. Pregnancy or lactating; note that a negative pregnancy test will be required if the patient is a female in reproductive years 7. Advanced liver, kidney, cardiac, or pulmonary disease as defined clinically or a terminal medical diagnosis consistent with survival \< 1 year 8. A history of significant alcohol or drug abuse in the prior six months 9. No focal cortical insult can be present, including tumor or vascular malformation 10. Patients may not be actively enrolled in a separate intervention study 11. Patients unable to undergo a brain MR: a. claustrophobia refractory to anxiolytics ferromagnetic metal in the body such as a prosthetic heart valve, a pacemaker, or a brain aneurysm clip). 12. Change in antipsychotic medication during the last 4 weeks 13. Any emergency psychiatry department visit during the last 4 weeks 14. Been an inpatient in a psychiatry clinic within the last month 15. Any other axis I diagnosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 3 weeks | Adverse event collection at baseline, daily for 5 days during treatment, every other day by phone until the final assessment at week 1 follow up visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive and Negative Syndrome Scale (PANSS) - Positive Subscale | Baseline, 5 days (post-treatment), 1 week post treatment | Potential therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) Positive Subscale, a 7 item subscale measuring the presence/absence and severity of positive symptoms of schizophrenia. The minimum score is 7 and the maximum score is 49, with higher values representing greater symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, and 1 week post treatment. The overall PANSS total score (minimum = 30, maximum = 210) is computed by summing the positive, negative, and general subscales; and higher values represent more severe schizophrenia psychopathology. |
| Positive and Negative Syndrome Scale (PANSS) - Negative Subscale | Baseline, 5 days (post-treatment), 1 week post treatment | Potential therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) Negative Subscale, a 7 item subscale measuring the presence/absence and severity of negative symptoms of schizophrenia. The minimum score is 7 and the maximum score is 49, with higher values representing greater symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, and 1 week post treatment. The overall PANSS total score (minimum = 30, maximum = 210) is computed by summing the positive, negative, and general subscales; and higher values represent more severe schizophrenia psychopathology. |
| Positive and Negative Syndrome Scale (PANSS) - General Subscale | Baseline, 5 days (post-treatment), 1 week post treatment | Potential therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) General Subscale, a 16 item subscale measuring the presence/absence and severity of general psychopathology of schizophrenia. The minimum score is 16 and the maximum score is 112, with higher values representing greater psychopathology severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, and 1 week post treatment. The overall PANSS total score (minimum = 30, maximum = 210) is computed by summing the positive, negative, and general subscales; and higher values represent more severe schizophrenia psychopathology. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Safety of rTMS in Schizophrenia Patients Participants will receive repetitive transcranial magnetic stimulation via MagPro x100 device to the vermis of cerebellum twice a day over 5 days
Transcranial magnetic stimulation via MagPro x100 device: Participants will receive 10 repetitive transcranial magnetic stimulation sessions to the vermis of cerebellum using the MagPro x100 TMS device. These 10 rTMS sessions will be administered from Monday to Friday in five days, twice a day with a minimum of 4-hour gap between the sessions. Repetitive TMS will be applied with the intermittent theta burst pattern (iTBS). These parameters are known to cause excitation in brain activity.
Anatomically precise localization of rTMS will be achieved using a frameless stereotactic system. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Safety of rTMS in Schizophrenia Patients |
|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 9.2 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Adverse Events
Adverse event collection at baseline, daily for 5 days during treatment, every other day by phone until the final assessment at week 1 follow up visit.
Time frame: 3 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety of rTMS in Schizophrenia Patients | Adverse Events | 1 event |
Secondary
Positive and Negative Syndrome Scale (PANSS) - General Subscale
Potential therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) General Subscale, a 16 item subscale measuring the presence/absence and severity of general psychopathology of schizophrenia. The minimum score is 16 and the maximum score is 112, with higher values representing greater psychopathology severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, and 1 week post treatment. The overall PANSS total score (minimum = 30, maximum = 210) is computed by summing the positive, negative, and general subscales; and higher values represent more severe schizophrenia psychopathology.
Time frame: Baseline, 5 days (post-treatment), 1 week post treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Safety of rTMS in Schizophrenia Patients | Positive and Negative Syndrome Scale (PANSS) - General Subscale | Before treatment (baseline) | 41.38 percentage of change | Standard Deviation 10.84 |
| Safety of rTMS in Schizophrenia Patients | Positive and Negative Syndrome Scale (PANSS) - General Subscale | Last day of treatment (after 5 days of treatment) | 39.13 percentage of change | Standard Deviation 11.81 |
| Safety of rTMS in Schizophrenia Patients | Positive and Negative Syndrome Scale (PANSS) - General Subscale | 1 week post treatment follow-up | 37 percentage of change | Standard Deviation 9.1 |
Secondary
Positive and Negative Syndrome Scale (PANSS) - Negative Subscale
Potential therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) Negative Subscale, a 7 item subscale measuring the presence/absence and severity of negative symptoms of schizophrenia. The minimum score is 7 and the maximum score is 49, with higher values representing greater symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, and 1 week post treatment. The overall PANSS total score (minimum = 30, maximum = 210) is computed by summing the positive, negative, and general subscales; and higher values represent more severe schizophrenia psychopathology.
Time frame: Baseline, 5 days (post-treatment), 1 week post treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Safety of rTMS in Schizophrenia Patients | Positive and Negative Syndrome Scale (PANSS) - Negative Subscale | Before treatment (baseline) | 23.75 percentage of change | Standard Deviation 6.92 |
| Safety of rTMS in Schizophrenia Patients | Positive and Negative Syndrome Scale (PANSS) - Negative Subscale | Last day of treatment (after 5 days of treatment) | 19.75 percentage of change | Standard Deviation 4.3 |
| Safety of rTMS in Schizophrenia Patients | Positive and Negative Syndrome Scale (PANSS) - Negative Subscale | 1 week post treatment follow-up | 19.88 percentage of change | Standard Deviation 5.82 |
Secondary
Positive and Negative Syndrome Scale (PANSS) - Positive Subscale
Potential therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) Positive Subscale, a 7 item subscale measuring the presence/absence and severity of positive symptoms of schizophrenia. The minimum score is 7 and the maximum score is 49, with higher values representing greater symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, and 1 week post treatment. The overall PANSS total score (minimum = 30, maximum = 210) is computed by summing the positive, negative, and general subscales; and higher values represent more severe schizophrenia psychopathology.
Time frame: Baseline, 5 days (post-treatment), 1 week post treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Safety of rTMS in Schizophrenia Patients | Positive and Negative Syndrome Scale (PANSS) - Positive Subscale | Before treatment (baseline) | 17.13 percentage of change | Standard Deviation 5.69 |
| Safety of rTMS in Schizophrenia Patients | Positive and Negative Syndrome Scale (PANSS) - Positive Subscale | Last day of treatment (after 5 days of treatment) | 17 percentage of change | Standard Deviation 5.93 |
| Safety of rTMS in Schizophrenia Patients | Positive and Negative Syndrome Scale (PANSS) - Positive Subscale | 1 week post treatment follow-up | 16.25 percentage of change | Standard Deviation 5.12 |