Trial Outcomes & Findings for Therapeutic Efficacy of Transcranial Magnetic Stimulation in Schizophrenia (NCT NCT01551979)

NCT ID: NCT01551979

Last Updated: 2018-04-12

Results Overview

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. Change from baseline on the PANSS Positive Subscale can range from -42 to +42; negative values represent an improvement in symptom severity, and positive values represent worsening symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

22 participants

Primary outcome timeframe

Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment

Results posted on

2018-04-12

Participant Flow

22 patients gave informed consent for the study during the initial screening visit. After patients were found ineligible to participate following review of medical records, withdrew consent, or were lost to follow-up, only 17 remained for the randomization phase and started the study.

Participant milestones

Participant milestones
Measure
Active rTMS
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Sham rTMS
Sham rTMS to the vermis (lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Overall Study
STARTED
10
7
Overall Study
Last Day of Treatment (After 5 Days)
10
7
Overall Study
1 Week Post Treatment
10
6
Overall Study
COMPLETED
8
5
Overall Study
NOT COMPLETED
2
2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Therapeutic Efficacy of Transcranial Magnetic Stimulation in Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Active rTMS
n=10 Participants
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Sham rTMS
n=7 Participants
Sham rTMS to the vermis (lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Total
n=17 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Age, Categorical
Between 18 and 65 years
10 Participants
n=93 Participants
7 Participants
n=4 Participants
17 Participants
n=27 Participants
Age, Categorical
>=65 years
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Sex: Female, Male
Female
2 Participants
n=93 Participants
2 Participants
n=4 Participants
4 Participants
n=27 Participants
Sex: Female, Male
Male
8 Participants
n=93 Participants
5 Participants
n=4 Participants
13 Participants
n=27 Participants
Region of Enrollment
United States
10 participants
n=93 Participants
7 participants
n=4 Participants
17 participants
n=27 Participants

PRIMARY outcome

Timeframe: Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment

Population: Participant drop out

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. Change from baseline on the PANSS Positive Subscale can range from -42 to +42; negative values represent an improvement in symptom severity, and positive values represent worsening symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.

Outcome measures

Outcome measures
Measure
Active rTMS
n=10 Participants
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Sham rTMS
n=7 Participants
Sham rTMS to the vermis (lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) Positive Subscale
5 days of treatment - baseline
-2.4 units on a scale
Standard Deviation 3.565
-1.857 units on a scale
Standard Deviation 1.574
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) Positive Subscale
1 week post treatment - baseline
-5.889 units on a scale
Standard Deviation 3.333
-3.667 units on a scale
Standard Deviation 3.724
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) Positive Subscale
3 week post treatment - baseline
-5 units on a scale
Standard Deviation 4.504
-3 units on a scale
Standard Deviation 3.317

PRIMARY outcome

Timeframe: Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment

Population: Participant drop out

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. Change from baseline on the PANSS Negative Subscale can range from -42 to +42; negative values represent an improvement in symptom severity, and positive values represent worsening symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.

Outcome measures

Outcome measures
Measure
Active rTMS
n=10 Participants
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Sham rTMS
n=7 Participants
Sham rTMS to the vermis (lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) Negative Subscale
5 days of treatment - baseline
-1 units on a scale
Standard Deviation 4.876
-1.571 units on a scale
Standard Deviation 2.070
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) Negative Subscale
1 week post treatment - baseline
-3.889 units on a scale
Standard Deviation 3.296
-1.667 units on a scale
Standard Deviation 3.141
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) Negative Subscale
3 week post treatment - baseline
-3.5 units on a scale
Standard Deviation 6.024
-0.2 units on a scale
Standard Deviation 4.604

PRIMARY outcome

Timeframe: Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment

Population: Participant drop out

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. Change from baseline on the PANSS General Subscale can range from -96 to +96; negative values represent an improvement in symptom severity, and positive values represent worsening symptom severity. Therapeutic efficacy was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.

Outcome measures

Outcome measures
Measure
Active rTMS
n=10 Participants
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Sham rTMS
n=7 Participants
Sham rTMS to the vermis (lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) General Subscale
5 days of treatment - baseline
-3.1 units on a scale
Standard Deviation 4.149
-2.714 units on a scale
Standard Deviation 5.090
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) General Subscale
1 week post treatment - baseline
-8.222 units on a scale
Standard Deviation 5.696
-2 units on a scale
Standard Deviation 4.690
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) General Subscale
3 week post treatment - baseline
-7.375 units on a scale
Standard Deviation 10.127
0 units on a scale
Standard Deviation 1

PRIMARY outcome

Timeframe: Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment

Population: Participant drop out

Treatment response was evaluated with the Clinical Global Impressions (CGI) Scale, which is comprised of two companion one-item measures that use 7-point scales to evaluate severity of psychopathology and improvement from the initiation of treatment; each component is rated separately and the CGI does not yield a global score. The CGI Severity of Illness is a 7-point subscale in which a clinician rates the severity of the patient's illness at the time of assessment. Ratings range from 1 to 7 and higher values represent more severe psychopathology: 1 indicates a normal and not at all ill patient and 7 indicates among the most extremely ill patients. Change from baseline on the CGI Severity of Illness subscale can range from -6 to +6, with negative values representing an improvement in psychopathology and positive values representing worsening psychopathology. Severity of Illness was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.

Outcome measures

Outcome measures
Measure
Active rTMS
n=10 Participants
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Sham rTMS
n=7 Participants
Sham rTMS to the vermis (lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Change From Baseline on the Clinical Global Impression (CGI) Severity of Illness
5 days of treatment - baseline
-0.3 units on a scale
Standard Deviation 0.483
-0.286 units on a scale
Standard Deviation 0.488
Change From Baseline on the Clinical Global Impression (CGI) Severity of Illness
1 week post treatment - baseline
-0.4 units on a scale
Standard Deviation 0.699
-0.5 units on a scale
Standard Deviation 0.548
Change From Baseline on the Clinical Global Impression (CGI) Severity of Illness
3 week post treatment - baseline
-0.5 units on a scale
Standard Deviation 0.535
-0.2 units on a scale
Standard Deviation 0.837

PRIMARY outcome

Timeframe: Last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment

Population: Participant drop out

Treatment response was evaluated with the Clinical Global Impressions (CGI) Scale, which is comprised of two companion one-item measures that use 7-point scales to evaluate severity of psychopathology and improvement from the initiation of treatment; each component is rated separately and the CGI does not yield a global score. The CGI Global Improvement is a 7-point subscale in which a clinician assesses how much a patient's illness has changed compared to baseline. Ratings range from 1 to 7, with 1 indicating very much improved and 7 indicating very much worse. Change from baseline on the CGI Global Improvement subscale can range from -6 to +6, with negative values representing an improvement in psychopathology and positive values representing worsening psychopathology. Global Improvement was assessed after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.

Outcome measures

Outcome measures
Measure
Active rTMS
n=10 Participants
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Sham rTMS
n=7 Participants
Sham rTMS to the vermis (lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Clinical Global Impression (CGI) Global Improvement
5 days of treatment
3.6 units on a scale
Standard Deviation 0.516
3.429 units on a scale
Standard Deviation 1.134
Clinical Global Impression (CGI) Global Improvement
1 week post treatment
3.3 units on a scale
Standard Deviation 0.675
4 units on a scale
Standard Deviation 0.632
Clinical Global Impression (CGI) Global Improvement
3 week post treatment
3.375 units on a scale
Standard Deviation 0.518
3.8 units on a scale
Standard Deviation 0.447

SECONDARY outcome

Timeframe: Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment

Population: Participant drop out

The Calgary Depression Scale for Schizophrenia is a 9-item scale that assesses depressive symptoms in patients with schizophrenia. Each item is rated separately and ratings range from 0 to 3. Higher values represent more severe depressive symptoms: 0 indicates an absent symptom and 3 indicates a severe symptom. The overall Calgary Depression Scale score is computed by summing each item. The total Calgary Depression Scale score ranges from 0 to 27, with higher values representing more severe depression in patients with schizophrenia. Change from baseline on the Calgary Depression Scale can range from -27 to +27, with negative values representing an improvement in depressive symptoms and positive values representing worsening depressive symptom severity. Depression was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.

Outcome measures

Outcome measures
Measure
Active rTMS
n=10 Participants
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Sham rTMS
n=7 Participants
Sham rTMS to the vermis (lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Change From Baseline on the Calgary Depression Scale for Schizophrenia
5 days of treatment - baseline
-2.6 units on a scale
Standard Deviation 3.204
-1.167 units on a scale
Standard Deviation 2.563
Change From Baseline on the Calgary Depression Scale for Schizophrenia
1 week post treatment - baseline
-2.7 units on a scale
Standard Deviation 2.908
-1.833 units on a scale
Standard Deviation 2.229
Change From Baseline on the Calgary Depression Scale for Schizophrenia
3 week post treatment - baseline
-2.25 units on a scale
Standard Deviation 2.121
0.8 units on a scale
Standard Deviation 2.387

Adverse Events

Active rTMS

Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths

Sham rTMS

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Active rTMS
n=10 participants at risk
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Sham rTMS
n=7 participants at risk
Sham rTMS to the vermis (lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Psychiatric disorders
Acute exacerbation of psychosis
10.0%
1/10 • Number of events 1 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
0.00%
0/7 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.

Other adverse events

Other adverse events
Measure
Active rTMS
n=10 participants at risk
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Sham rTMS
n=7 participants at risk
Sham rTMS to the vermis (lobule VII) of the cerebellum. Repetitive Transcranial Magnetic Stimulation: intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
Nervous system disorders
Discomfort with TMS
10.0%
1/10 • Number of events 1 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
0.00%
0/7 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
Cardiac disorders
Blood pressure increase
10.0%
1/10 • Number of events 1 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
0.00%
0/7 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
Nervous system disorders
Headache
20.0%
2/10 • Number of events 2 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
14.3%
1/7 • Number of events 2 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
Skin and subcutaneous tissue disorders
Scalp pain
0.00%
0/10 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
14.3%
1/7 • Number of events 2 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
Musculoskeletal and connective tissue disorders
Neck pain
30.0%
3/10 • Number of events 4 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
14.3%
1/7 • Number of events 1 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
Musculoskeletal and connective tissue disorders
Head heaviness
10.0%
1/10 • Number of events 3 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
0.00%
0/7 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
Nervous system disorders
Change in energy level
10.0%
1/10 • Number of events 2 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
0.00%
0/7 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
Psychiatric disorders
Change in mood
10.0%
1/10 • Number of events 1 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.
0.00%
0/7 • 4 weeks (5 days of treatment and 1 week and 3 weeks post treatment)
0 total number of participants at risk for all-cause mortality because all-cause mortality was not collected/assessed.

Additional Information

Mark Halko

Beth Israel Deaconess Medical Center

Phone: 6176670367

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place