SchizophreniaNCT02642029

Targeting Cerebellum to Treat Psychosis: a Transcranial Magnetic Stimulation (TMS) Study

A study testing Excitatory TMS and Inhibitory TMS in people with Schizophrenia and Schizoaffective Disorder, run by Mclean Hospital at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Schizophrenia, Schizoaffective Disorder, Bipolar Disorder I
What is being tested?: Excitatory TMS and Inhibitory TMS
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 28 participants
Where: 2 sitesUnited States
Study dates: 18 Feb 2016to 14 Jun 2019
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Patients
Men and women
Ages 18-50 years
Patients diagnosed with schizophrenia (SZ), schizoaffective disorder (SZA), or psychotic bipolar disorder (BP).
On a stable psychiatric medication regimen for at least a month prior to and during study participation
Healthy Controls:

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Men and women
Ages 18-50 years
Without major psychiatric illness

Who cannot join

Patients
Any change in psychiatric medications within a month prior to and during study participation
Legal or mental incompetency
Intellectual disability
Substance use disorder (abuse or dependence) with active use within the last 3 months
Significant medical or neurological illness

Show all 46Show fewer

Prior neurosurgical procedure
History of seizures
History of electroconvulsive therapy (ECT) or clinical TMS within the past three months
History of participation in a cerebellar TMS study
Implanted cardiac pacemakers
Patients who have conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head or neck, or are non-removable and within 30 cm of the treatment coil. These include:
Aneurysm clips or coils
Carotid or cerebral stents
Metallic devices implanted in the head (e.g. Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, or ventriculo-peritoneal shunt)
Magnetically active dental implants
Cochlear/otologic implants
CSF shunts
Ferromagnetic ocular implants
Pellets, bullets, fragments less than 30 cm from the coil
Facial tattoos with metallic ink, permanent makeup less than 30 cm from the coil
Pregnant women
Healthy Controls:
History of major psychiatric illness, including psychosis
Has a first-degree relative with psychosis
Active use of psychotropic medications
Legal or mental incompetency
Intellectual disability
Substance use disorder (abuse or dependence) with active use within the last 3 months
Significant medical or neurological illness
Prior neurosurgical procedure
History of seizures
History of ECT treatment or clinical TMS within the past three months
History of participation in a cerebellar TMS study
Implanted cardiac pacemakers
Individuals who have conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head or neck, or are non-removable and within 30 cm of the treatment coil. These include:
Aneurysm clips or coils
Carotid or cerebral stents
Metallic devices implanted in the head (e.g. Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, transcutaneous electrical nerve stimulation (TENS) unit, or ventriculo-peritoneal shunt)
Magnetically active dental implants
Cochlear/otologic implants
Cerebrospinal fluid (CSF) shunts
Ferromagnetic ocular implants
Pellets, bullets, fragments less than 30 cm from the coil
Facial tattoos with metallic ink, permanent makeup less than 30 cm from the coil
Pregnant women

Trial locations and contacts

2 sites in 1 country.

United States2 sites

McLean Hospital
Belmont, Massachusetts, 02478
Massachusetts General Hospital
Charlestown, Massachusetts, 02129

Other trials in United States

About this study

Official title: Cerebellar Transcranial Magnetic Stimulation (cTMS) in Psychotic Disorders: Effect on Time Perception, Executive Function, and Mood and Psychotic Symptoms

The goal of this study is to use transcranial magnetic stimulation (TMS) to investigate the impact of modulating cerebellar activity on time perception, executive function, and mood and psychotic symptoms in psychosis patients (i.e., schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features). The investigators hypothesize that abnormally reduced activity in the cerebellum contributes to the abnormalities in patients, that cerebellum-mediated disruptions in time perception may partially underlie executive dysfunction and symptoms, and that cerebellar stimulation will normalize disease-relevant outcome measures.

Read the detailed description

The cerebellum plays a major role in integrative processing of higher order cognitive and affective functions, but it has not been considered a major treatment target for psychotic disorders. The goal of this study is to administer three different conditions of transcranial magnetic stimulation (TMS)-- excitatory, inhibitory, and sham TMS-- in a cross-over design in psychosis patients (i.e., schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features) to investigate with causal explanatory power the role of the cerebellum as a treatment target for psychotic disorders. More specifically, the investigators will measure the effects of cerebellar excitation and inhibition on time perception, executive function, and symptomatology. TMS will be administered using a theta-burst stimulation (TBS) protocol applied to the posterior cerebellar vermis. Participants will undergo three study sessions, one for each of the three TMS conditions. During each session, the investigators will administer validated cognitive paradigms and clinical measures immediately before and after TMS.

The specific aims are to:

1: Investigate the role of the cerebellum in abnormalities of time perception, executive function, and mood and psychotic symptoms by evaluating these functions before and immediately after excitatory, inhibitory, or sham TMS applied to the cerebellar vermis in patients with psychosis.

(1a) Time perception hypothesis: Patients with psychotic disorders will have impaired timing perception, i.e., higher number of errors and/or greater inter-trial variability in an interval discrimination task both at baseline and after sham TMS. The investigators predict that the abnormalities in patients will improve after excitatory but not inhibitory TMS.

(1b) Executive function hypothesis: Patients will show a higher number of errors and longer reaction times on the N-back working memory task, both at baseline and after sham TMS. The investigators predict that these deficits in patients will improve after excitatory but not inhibitory TMS.

(1c) Symptom hypothesis: Symptom ratings using visual analog scales will improve in the period immediately after excitatory but not inhibitory TMS, and show no significant change after sham TMS.

2: Investigate the relationship between time perception and symptomatology in patients with psychotic disorders. Hypothesis: The investigators predict that performance on the time perception task will correlate with performance on a working memory task as well as with mood and psychotic symptoms.

This study may improve understanding about the role of the cerebellum in the pathophysiology of psychotic disorders. Such knowledge can potentially guide the development of cerebellar TMS as a therapeutic intervention for psychosis.

Conditions: Schizophrenia, Schizoaffective Disorder, Bipolar Disorder I
Being tested: Excitatory TMS, Inhibitory TMS, Sham TMS
Keywords: time perception, executive function, psychosis, mood symptoms
Medical subject headings: Schizophrenia, Psychotic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Excitatory TMSDevice
Also called iTBS
Single session of intermittent theta-burst stimulation (600 pulses in blocks of 2s, separated by 8s of pause) to cerebellar vermis.
Inhibitory TMSDevice
Also called cTBS
Single session of continuous theta-burst stimulation of 600 pulses to cerebellar vermis.
Sham TMSDevice
Also called shamTBS
Single session, using the exact same procedures as the active arms but with a sham coil, which is designed to induce the same nonspecific sensory effects of TMS (auditory and somatosensory activation) without inducing the neuromodulatory magnetic fields.

Study groups in NCT02642029
Study group	Role	What they receive
Intermittent TBS (iTBS)	Experimental	Single session of intermittent theta-burst stimulation (600 pulses in blocks of 2s, separated by 8s of pause) to cerebellar vermis. Receives: Device: Excitatory TMS
Continuous TBS (cTBS)	Active comparator	Single session of continuous theta-burst stimulation of 600 pulses to cerebellar vermis. Receives: Device: Inhibitory TMS
Sham TBS	Sham comparator	Single session, using the exact same procedures as the active arms but with a sham coil, which is designed to induce the same nonspecific sensory effects of TMS (auditory and somatosensory activation) without inducing the neuromodulatory magnetic fields. Receives: Device: Sham TMS

What is being measured

The primary outcome is the main question the study is designed to answer.

Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS
In each trial, participants are presented with two tones separated by 1200 ms (the standard interval), a 1s delay, then a comparison pair of tones. The time interval of the second tone pair will be either equal to (E-condition), longer than (L-condition), or shorter than (S-condition) that of the first pair. Participants are asked to indicate using a keyboard whether the second time interval is equal, longer, or shorter than the first. The tones for all conditions were 700Hz in frequency, 50ms in duration, and presented binaurally via headphones. Participants completed 15 trials during each pre- or post-TMS session for a total of up to 90 total trials across the three study visits. Prior to each IDT session, participants performed a practice run consisting of six trials. The primary outcome for this task was overall accuracy (proportion of correct responses).
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS
Participants are presented with a series of words or numbers and prompted to indicate as quickly as possible whether the currently presented stimulus is the same as the one presented n-stimuli previously. For example, in a 2-back task a subject would be asked to indicate whether the current stimulus was identical to that presented 2 stimuli before. To increase the likelihood of detecting change in task performance with each TMS condition (and minimize potential ceiling or floor effects), the difficulty level was individualized so that each participant performed at approximately 80% accuracy; during the "pre" session of the first study visit, a trial session established the difficulty level, i.e., how many presentations back (n-stimuli) at which the task would start. After the trial session, a session with 50 presentations was carried out and recorded whether the response was correct (accuracy) and the time from presentation to response (reaction time).
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS
Participants are presented with a series of words or numbers and prompted to indicate as quickly as possible whether the currently presented stimulus is the same as the one presented n-stimuli previously. For example, in a 2-back task a subject would be asked to indicate whether the current stimulus was identical to that presented 2 stimuli before. To increase the likelihood of detecting change in task performance with each TMS condition (and minimize potential ceiling or floor effects), the difficulty level was individualized so that each participant performed at approximately 80% accuracy; during the "pre" session of the first study visit, a trial session established the difficulty level, i.e., how many presentations back (n-stimuli) at which the task would start. After the trial session, a session with 50 presentations was carried out and recorded whether the response was correct (accuracy) and the time from presentation to response (reaction time).
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Change (Δ) in Symptoms (Depressed Mood)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Change (Δ) in Symptoms (Anxiety)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Change (Δ) in Symptoms (Elated Mood)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent/no elation, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. Higher VAS scores for elation indicate more elation (suggestive of mania). The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Change (Δ) in Symptoms (Auditory Hallucinations)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Change (Δ) in Symptoms (Visual Hallucinations)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Change (Δ) in Symptoms (Paranoid Ideation)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Change (Δ) in Symptoms (Ideas/Delusions of Reference)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Change (Δ) in Symptoms (Delusions of Control)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Measured: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Feb 201614 Jun 2019

First posted30 Dec 2015 (estimated)
Study start18 Feb 2016
Primary completion14 Jun 2019
Study completion14 Jun 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for SchizophreniaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02642029
Sponsor's protocol ID: 2015P001833
Status last verified: Dec 2022
First submitted: 20 Nov 2015
Last updated: 30 Dec 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Shinn AK, Hurtado-Puerto AM, Roh YS, Ho V, Hwang M, Cohen BM, Ongur D, Camprodon JA. Cerebellar transcranial magnetic stimulation in psychotic disorders: intermittent, continuous, and sham theta-burst stimulation on time perception and symptom severity. Front Psychiatry. 2023 Nov 13;14:1218321. doi: 10.3389/fpsyt.2023.1218321. eCollection 2023.
PubMed 38025437

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 30 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Cerebellar Transcranial Magnetic Stimulation (cTMS) in Psychotic Disorders: Effect on Time Perception, Executive Function, and Mood and Psychotic Symptoms
ClinicalTrials.gov ID: NCT02642029
Acronym / sponsor ID: 2015P001833
Conditions: Schizophrenia, Schizoaffective Disorder, Bipolar Disorder I
Keywords: time perception, executive function, psychosis, mood symptoms
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Mclean HospitalUniversity, hospital or other
Collaborators: Massachusetts General Hospital
Study start: 18 Feb 2016 (actual)
Primary completion: 14 Jun 2019 (actual)
Study completion: 14 Jun 2019 (actual)
First posted: 30 Dec 2015 (estimated)
Results: Posted 30 Dec 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The specific aims are to:

(1c) Symptom hypothesis: Symptom ratings using visual analog scales will improve in the period immediately after excitatory but not inhibitory TMS, and show no significant change after sham TMS.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Intermittent TBS (iTBS)	Experimental	Device: Excitatory TMSSingle session of intermittent theta-burst stimulation (600 pulses in blocks of 2s, separated by 8s of pause) to cerebellar vermis.
Continuous TBS (cTBS)	Active comparator	Device: Inhibitory TMSSingle session of continuous theta-burst stimulation of 600 pulses to cerebellar vermis.
Sham TBS	Sham comparator	Device: Sham TMSSingle session, using the exact same procedures as the active arms but with a sham coil, which is designed to induce the same nonspecific sensory effects of TMS (auditory and somatosensory activation) without inducing the neuromodulatory magnetic fields.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 listed)

Patients
Healthy Controls:

Key exclusion criteria (46 listed)

Patients
Healthy Controls:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Excitatory TMSAlso: iTBSSingle session of intermittent theta-burst stimulation (600 pulses in blocks of 2s, separated by 8s of pause) to cerebellar vermis.	Device	Intermittent TBS (iTBS)
Inhibitory TMSAlso: cTBSSingle session of continuous theta-burst stimulation of 600 pulses to cerebellar vermis.	Device	Continuous TBS (cTBS)
Sham TMSAlso: shamTBSSingle session, using the exact same procedures as the active arms but with a sham coil, which is designed to induce the same nonspecific sensory effects of TMS (auditory and somatosensory activation) without inducing the neuromodulatory magnetic fields.	Device	Sham TBS

Primary outcome

Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
In each trial, participants are presented with two tones separated by 1200 ms (the standard interval), a 1s delay, then a comparison pair of tones. The time interval of the second tone pair will be either equal to (E-condition), longer than (L-condition), or shorter than (S-condition) that of the first pair. Participants are asked to indicate using a keyboard whether the second time interval is equal, longer, or shorter than the first. The tones for all conditions were 700Hz in frequency, 50ms in duration, and presented binaurally via headphones. Participants completed 15 trials during each pre- or post-TMS session for a total of up to 90 total trials across the three study visits. Prior to each IDT session, participants performed a practice run consisting of six trials. The primary outcome for this task was overall accuracy (proportion of correct responses).
Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Participants are presented with a series of words or numbers and prompted to indicate as quickly as possible whether the currently presented stimulus is the same as the one presented n-stimuli previously. For example, in a 2-back task a subject would be asked to indicate whether the current stimulus was identical to that presented 2 stimuli before. To increase the likelihood of detecting change in task performance with each TMS condition (and minimize potential ceiling or floor effects), the difficulty level was individualized so that each participant performed at approximately 80% accuracy; during the "pre" session of the first study visit, a trial session established the difficulty level, i.e., how many presentations back (n-stimuli) at which the task would start. After the trial session, a session with 50 presentations was carried out and recorded whether the response was correct (accuracy) and the time from presentation to response (reaction time).
Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Participants are presented with a series of words or numbers and prompted to indicate as quickly as possible whether the currently presented stimulus is the same as the one presented n-stimuli previously. For example, in a 2-back task a subject would be asked to indicate whether the current stimulus was identical to that presented 2 stimuli before. To increase the likelihood of detecting change in task performance with each TMS condition (and minimize potential ceiling or floor effects), the difficulty level was individualized so that each participant performed at approximately 80% accuracy; during the "pre" session of the first study visit, a trial session established the difficulty level, i.e., how many presentations back (n-stimuli) at which the task would start. After the trial session, a session with 50 presentations was carried out and recorded whether the response was correct (accuracy) and the time from presentation to response (reaction time).
Change (Δ) in Symptoms (Depressed Mood)
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Change (Δ) in Symptoms (Anxiety)
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Change (Δ) in Symptoms (Elated Mood)
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent/no elation, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. Higher VAS scores for elation indicate more elation (suggestive of mania). The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Change (Δ) in Symptoms (Auditory Hallucinations)
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Change (Δ) in Symptoms (Visual Hallucinations)
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Change (Δ) in Symptoms (Paranoid Ideation)
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Change (Δ) in Symptoms (Ideas/Delusions of Reference)
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Change (Δ) in Symptoms (Delusions of Control)
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.

Results and safety

Results posted to the registry on 30 Dec 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sham-iTBS-cTBS	6	6
Sham-cTBS-iTBS	5	5
iTBS-sham-cTBS	3	3
iTBS-cTBS-sham	4	4
cTBS-sham-iTBS	4	4
cTBS-iTBS-sham	4	4

Primary outcome: Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS

Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.. Mean (Standard Deviation). Unit: accuracy (proportion correct)

Measure	Intermittent TBS (iTBS) n = 22	Continuous TBS (cTBS) n = 21	Sham TBS n = 25
Pre-TBS	.503 (.156)	.521 (.183)	.456 (.141)
Post-TBS	.479 (.128)	.514 (.145)	.525 (.174)
Change in accuracy (post-pre)	-.024 (.175)	-.006 (.163)	.069 (.198)

Intermittent TBS (iTBS) vs Sham TBS: Beta coefficient for timexiTBS interact: -.099 (95% CI -.1989 to .0002), p = 0.51, Mixed Models Analysis
Continuous TBS (cTBS) vs Sham TBS: Beta coefficient for timexcTBS interact: -.0757 (95% CI -.1770 to .0256), p = 0.143, Mixed Models Analysis

Population analysed: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for "overall number of participants analyzed" (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).

Primary outcome: Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS

Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.. Least squares mean (Standard Error). Unit: accuracy (proportion correct)

Measure	Intermittent TBS (iTBS) n = 22	Continuous TBS (cTBS) n = 21	Sham TBS n = 25
Pre-TBS	0.780 (0.0144)	0.753 (0.0156)	0.775 (0.0143)
Post-TBS	0.795 (0.0138)	0.778 (0.0147)	0.784 (0.0139)
Ratio (post/pre)	1.10 (.074)	1.15 (.077)	1.05 (.065)

Intermittent TBS (iTBS) vs Sham TBS: Beta coefficient for timexiTBS interact: -.0446, p = .626, Mixed Models Analysis
Continuous TBS (cTBS) vs Sham TBS: Beta coefficient for timexcTBS interact: -0.0903, p = 0.322, Mixed Models Analysis

Primary outcome: Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS

Measure	Intermittent TBS (iTBS) n = 22	Continuous TBS (cTBS) n = 21	Sham TBS n = 25
Pre-TBS	831 (13.29)	862 (14.62)	901 (11.63)
Post-TBS	817 (10.66)	886 (10.80)	877 (9.16)
Change in RT (post-pre)	-14 (8.90)	24.0 (11.46)	-23.8 (7.41)

Intermittent TBS (iTBS) vs Continuous TBS (cTBS) vs Sham TBS: Beta coefficient for timexiTBS interact: -9.797, p = 0.1118, Mixed Models Analysis
Intermittent TBS (iTBS) vs Continuous TBS (cTBS) vs Sham TBS: Beta coefficient for timexcTBS interact: -47.764, p = 0.00000009, Mixed Models Analysis

Primary outcome: Change (Δ) in Symptoms (Depressed Mood)

Measure	Intermittent TBS (iTBS) n = 22	Continuous TBS (cTBS) n = 21	Sham TBS n = 25
Pre-TBS	22.5 (0 to 70)	37 (0 to 91)	16 (0 to 70)
Post-TBS	19.5 (0 to 72)	42 (0 to 71)	4 (0 to 76)
Change in VAS score (post-pre)	0 (-31 to 63)	0 (-41 to 26)	0 (-43 to 7)

Intermittent TBS (iTBS) vs Continuous TBS (cTBS) vs Sham TBS: p = 0.910, Friedman test
Intermittent TBS (iTBS) vs Continuous TBS (cTBS) vs Sham TBS: beta coefficient for depressed mood: 0.00071 (95% CI -0.00048 to 0.00190), p = 0.243, Mixed Models Analysis

Adverse events

Time frame: Varied. Approximately one-month time frame (mean 11.6 ± 6.6, range 4-28 days). Participants were monitored for adverse events from enrollment to end of study participation.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Intermittent TBS (iTBS)	0 of 22 (0%)	2 of 22 (9.1%)	0 of 22
Continuous TBS (cTBS)	0 of 21 (0%)	0 of 21 (0%)	0 of 21
Sham TBS	0 of 25 (0%)	1 of 25 (4%)	0 of 25

Limitations and caveats (from the sponsor): (1) Small sample size. (2) Statistical analyses uncorrected for multiple comparisons. (3) Sample consisted mostly of stable outpatients with low symptom severity. (4) IDT task difficulty was not adjusted to participant performance. (5) Negative symptoms were not evaluated. However, acute changes in negative symptoms (which tend to be trait-like phenomena) are more challenging to measure. (6) Study did not include any biological markers (e.g., imaging) by which to measure TBS effects.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38025437Shinn AK, Hurtado-Puerto AM, Roh YS, Ho V, Hwang M, Cohen BM, Ongur D, Camprodon JA. Cerebellar transcranial magnetic stimulation in psychotic disorders: intermittent, continuous, and sham theta-burst stimulation on time perception and symptom severity. Front Psychiatry. 2023 Nov 13;14:1218321. doi: 10.3389/fpsyt.2023.1218321. eCollection 2023.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ann K Shinn, MD, MPH principal investigator

Mclean Hospital

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Excitatory TMS and Inhibitory TMS in people with Schizophrenia and Schizoaffective Disorder, run by Mclean Hospital at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS (time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02642029, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2022.