Trial Outcomes & Findings for Using Transcranial Magnetic Stimulation (TMS) to Understand 'Negative' Symptoms of Schizophrenia (NCT NCT03648268)
NCT ID: NCT03648268
Last Updated: 2026-06-25
Results Overview
We will evaluate the effect of sham vs active rTMS on The Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Negative Symptom total score. This score is the sum of seven questions on the PANSS questionnaire (named N1-N7). Each question is scored from 1-7 for a total score per individual ranging from 7-49. On this scale higher numbers indicate great symptomology
Recruitment status
TERMINATED
Study phase
NA
Target enrollment
47 participants
Primary outcome timeframe
Before treatment (Baseline) and 1 week post treatment
Results posted on
2026-06-25
Participant Flow
47 participants agreed to participate in the study following completion of the informed consent process. During subsequent study procedures, 18 consented participants were found ineligible to continue in the study and were not randomized to a treatment arm. Participants were randomized into "Active Cerebellum rTMS" and "Sham Cerebellum rTMS" arms but the study concluded before participants could be enrolled into the "Active DLPFC rTMS" and "Sham DLPFC rTMS"
Participant milestones
| Measure |
Active Cerebellum rTMS
Active repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum at 100% of active motor threshold.
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
Sham Cerebellum rTMS
Sham repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
16
|
|
Overall Study
COMPLETED
|
13
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Using Transcranial Magnetic Stimulation (TMS) to Understand 'Negative' Symptoms of Schizophrenia
Baseline characteristics by cohort
| Measure |
Active Cerebellum rTMS
n=13 Participants
Active repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum at 100% of active motor threshold.
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
Sham Cerebellum rTMS
n=16 Participants
Sham repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
Total
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
35.8 years
STANDARD_DEVIATION 7.7 • n=20 Participants
|
36.6 years
STANDARD_DEVIATION 12 • n=20 Participants
|
36.3 years
STANDARD_DEVIATION 10.1 • n=40 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=20 Participants
|
5 Participants
n=20 Participants
|
7 Participants
n=40 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=20 Participants
|
11 Participants
n=20 Participants
|
22 Participants
n=40 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
4 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=20 Participants
|
3 Participants
n=20 Participants
|
4 Participants
n=40 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=20 Participants
|
11 Participants
n=20 Participants
|
17 Participants
n=40 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
4 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Region of Enrollment
United States
|
13 Participants
n=20 Participants
|
16 Participants
n=20 Participants
|
29 Participants
n=40 Participants
|
|
PANSS negative symptoms total
|
14.69 PANSS negative symptoms total
STANDARD_DEVIATION 4.75 • n=20 Participants
|
15.44 PANSS negative symptoms total
STANDARD_DEVIATION 4.242 • n=20 Participants
|
15.1 PANSS negative symptoms total
STANDARD_DEVIATION 4.4 • n=40 Participants
|
|
PANSS P3 Hallucination Severity
|
2.77 units on a scale
STANDARD_DEVIATION 1.88 • n=20 Participants
|
2.75 units on a scale
STANDARD_DEVIATION 1.88 • n=20 Participants
|
2.76 units on a scale
STANDARD_DEVIATION 1.84 • n=40 Participants
|
PRIMARY outcome
Timeframe: Before treatment (Baseline) and 1 week post treatmentWe will evaluate the effect of sham vs active rTMS on The Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Negative Symptom total score. This score is the sum of seven questions on the PANSS questionnaire (named N1-N7). Each question is scored from 1-7 for a total score per individual ranging from 7-49. On this scale higher numbers indicate great symptomology
Outcome measures
| Measure |
Active Cerebellum rTMS
n=13 Participants
Active repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum at 100% of active motor threshold.
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
Sham Cerebellum rTMS
n=16 Participants
Sham repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
|---|---|---|
|
Change in Negative Symptom Severity
|
-0.77 change in PANSS negative symptom total
Standard Deviation 1.92
|
-0.5 change in PANSS negative symptom total
Standard Deviation 2.22
|
SECONDARY outcome
Timeframe: Before treatment (Baseline) and 1 week post treatmentPopulation: Individuals who completed the rTMS intervention and underwent resting-state fMRI scanning before and after intervention. Functional connectivity is calculated as the fisher's z-transformed Pearson's correlation coefficient of BOLD signal between posterior cerebellum and right DLPFC ROIs. Change in connectivity is calculated as the connectivity value at baseline subtracted from the value at follow-up.
We will evaluate the effect of sham vs active rTMS on cerebellar-prefrontal cortex functional connectivity in the group with Cerebellar targeted rTMS and in the group with DLPFC targeted rTMS
Outcome measures
| Measure |
Active Cerebellum rTMS
n=12 Participants
Active repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum at 100% of active motor threshold.
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
Sham Cerebellum rTMS
n=13 Participants
Sham repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
|---|---|---|
|
Change in Cerebellar - Prefrontal Functional Connectivity
|
-.148 Pearson's correlation coefficient
Standard Deviation .241
|
.087 Pearson's correlation coefficient
Standard Deviation .171
|
SECONDARY outcome
Timeframe: Before treatment (Baseline) and 1 week post treatmentWe will evaluate the effect of sham vs active rTMS on the frequency and severity of auditory hallucinations in the group with Cerebellar targeted rTMS. PANSS P3 Hallucination Severity is a single question on the Positive and Negative Syndrome Scale. Question P3 assesses hallucination severity and ranges from 1 (least symptomatic) to 7 (most symptomatic)
Outcome measures
| Measure |
Active Cerebellum rTMS
n=13 Participants
Active repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum at 100% of active motor threshold.
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
Sham Cerebellum rTMS
n=16 Participants
Sham repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
|---|---|---|
|
Change in Auditory Hallucination Severity
|
-.08 change in PANSS question P3
Standard Deviation .86
|
-.18 change in PANSS question P3
Standard Deviation .40
|
Adverse Events
Active Cerebellum rTMS
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Sham Cerebellum rTMS
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Active Cerebellum rTMS
n=13 participants at risk
Active repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum at 100% of active motor threshold.
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
Sham Cerebellum rTMS
n=16 participants at risk
Sham repetitive Transcranial Magnetic Stimulation (rTMS) with iTBS pattern to the cerebellum
repetitive Transcranial Magnetic Stimulation (rTMS): rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of TMS with fMRI allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.
The pattern of rTMS will consist of either:
intermittent Theta Burst Stimulation (iTBS) pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
OR
sham stimulation
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
headache/neck pain
|
53.8%
7/13 • 2 weeks
Adverse events are reported for "Active Cerebellum rTMS" and "Sham Cerebellum rTMS" arms but the study concluded before participants could be enrolled into the "Active DLPFC rTMS" and "Sham DLPFC rTMS"
|
56.2%
9/16 • 2 weeks
Adverse events are reported for "Active Cerebellum rTMS" and "Sham Cerebellum rTMS" arms but the study concluded before participants could be enrolled into the "Active DLPFC rTMS" and "Sham DLPFC rTMS"
|
|
Skin and subcutaneous tissue disorders
skin irritation
|
15.4%
2/13 • 2 weeks
Adverse events are reported for "Active Cerebellum rTMS" and "Sham Cerebellum rTMS" arms but the study concluded before participants could be enrolled into the "Active DLPFC rTMS" and "Sham DLPFC rTMS"
|
0.00%
0/16 • 2 weeks
Adverse events are reported for "Active Cerebellum rTMS" and "Sham Cerebellum rTMS" arms but the study concluded before participants could be enrolled into the "Active DLPFC rTMS" and "Sham DLPFC rTMS"
|
Additional Information
Roscoe Brady MD, PhD
Beth Israel Deaconess Medical Center
Phone: 617-632-7933
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place