SchizophreniaNCT05343598
Using Transcranial Magnetic Stimulation (TMS) to Understand Hallucinations in Schizophrenia
A study testing Repetitive Transcranial Magnetic Stimulation (rTMS) in people with Schizophrenia and Schizo Affective Disorder, run by Mclean Hospital at 1 site in United States.
Trial summary
This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study how hallucinations work in schizophrenia. TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia, Schizo Affective Disorder
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation (rTMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2021to 31 Oct 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of schizophrenia or schizoaffective disorder
Who cannot join
- substance use disorder in past 3 months
- ambidexterity
- contraindications for TMS or MRI including :
- history of neurological disorder
- history of head trauma resulting in loss of consciousness
- history of seizures or diagnosis of epilepsy or first degree relative family history of epilepsy
Show all 9Show fewer
- metal in brain or skull
- implanted devices such as a pacemaker, medication pump, nerve stimulator or ventriculoperitoneal shunt
- claustrophobic in MRI
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Mark Halko, PhD contact
United States1 site, 1 recruiting
- Recruiting
McLean Hospital
Belmont, Massachusetts, 02478
About this study
Official title: Empirical Validation of a Cerebellar-cortical Hallucination Circuit
This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study how hallucinations work in schizophrenia.
TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study the investigators will be stimulating the brain to learn more about how TMS might improve these symptoms of schizophrenia.
Read the detailed description
This study tests the hypothesis that hallucinations in schizophrenia are mediated by network pathophysiology, and that network pathophysiology can be quantified by the functional connectivity of a cerebellar-thalamo-cortical circuit. To accomplish this, participants will be recruited who are diagnosed with schizophrenia or schizoaffective disorder who experience auditory hallucinations.
Participants will undergo an initial screening session to complete informed consent and undergo baseline assessments of schizophrenia symptom severity. These assessments include reporter-based measures such as the Positive and Negative Syndrome Scale (PANSS).
Participants will then undergo an MRI scan that includes structural and resting-state functional magnetic resonance imaging (rsfMRI). These rsfMRI imagines will be used to isolate individual resting state networks for targeting of rTMS modulation.
Participants will then undergo five days of twice daily rTMS sessions.
One week after the last rTMS session, participants will undergo follow-up MRI imaging and the same study assessments.
- Conditions
- Schizophrenia, Schizo Affective Disorder
- Being tested
- Repetitive Transcranial Magnetic Stimulation (rTMS), Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
- 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.
Repetitive Transcranial Magnetic Stimulation (rTMS)Device
Also called iTBS
rTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry.
The rTMS pulses will be delivered in a pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz every 10s for 600 total pulses.
Sham Repetitive Transcranial Magnetic Stimulation (rTMS)Device
Also called iTBS
rTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry.
The rTMS pulses will be delivered in a pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz every 10s for 600 total pulses.
Sham is achieved by using a coil with a magnetic shield preventing magnetic field from reaching the head.
| Study group | Role | What they receive |
|---|---|---|
| Active cerebellum rTMS | Active comparator | Cerebellar targeted iTBS, twice daily, one week. Receives: Device: Repetitive Transcranial Magnetic Stimulation (rTMS) |
| Sham cerebellum rTMS | Sham comparator | Cerebellar targeted sham iTBS, twice daily, one week. Receives: Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
functional connectivity
change in functional connectivity of a putative cerebellar-thalamic-cortical hallucination circuit (cerebellum to thalamus) will be assessed before and after (1 week followup) TMS stimulation.
Measured: baseline, 1 week after TMS
Positive and Negative Syndrome Scale (PANSS)
The PANSS is clinical rating scale of symptom severity . Each descriptor is rated on a 7 point scale from 1=(absence of any symptom) to 7=(extremely severe symptoms).
Measured: baseline
Scale for the Assessment of Positive Symptoms (SAPS)
The SAPS is clinical rating scale of symptom severity . Each descriptor is rated on a 5 point scale from 1=(absence of any symptom) to 5=(extremely severe symptoms).
Measured: baseline
Auditory Hallucination Rating Scale (AHRS) Scale (AHRS)
The AHRS is a 7-item clinical rating scale used to assess auditory hallucinations.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2022
- Study start13 Oct 2021
- Primary completion31 Oct 2026 (estimated)
- Study completion31 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mark A. Halko, PhD, Mclean Hospital
- Investigators
- Mark Halko, PhD, Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05343598
- Sponsor's protocol ID
- 2021P002459
- Other IDs
- R01MH126000
- Status last verified
- Jan 2026
- First submitted
- 13 Apr 2022
- Last updated
- 22 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: deidentified participant data will be shared with NIMH Data Repository (NDA).
Publications
Brady RO Jr, Gonsalvez I, Lee I, Ongur D, Seidman LJ, Schmahmann JD, Eack SM, Keshavan MS, Pascual-Leone A, Halko MA. Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia. Am J Psychiatry. 2019 Jul 1;176(7):512-520. doi: 10.1176/appi.ajp.2018.18040429. Epub 2019 Jan 30.
PubMed 30696271Basavaraju R, Ithal D, Thanki MV, Ramalingaiah AH, Thirthalli J, Reddy RP, Brady RO Jr, Halko MA, Bolo NR, Keshavan MS, Pascual-Leone A, Mehta UM, Kesavan M. Intermittent theta burst stimulation of cerebellar vermis enhances fronto-cerebellar resting state functional connectivity in schizophrenia with predominant negative symptoms: A randomized controlled trial. Schizophr Res. 2021 Dec;238:108-120. doi: 10.1016/j.schres.2021.10.005. Epub 2021 Oct 12.
PubMed 34653740Nawaz U, Lee I, Beermann A, Eack S, Keshavan M, Brady R. Individual Variation in Functional Brain Network Topography is Linked to Schizophrenia Symptomatology. Schizophr Bull. 2021 Jan 23;47(1):180-188. doi: 10.1093/schbul/sbaa088.
PubMed 32648915Hwang M, Roh YS, Talero J, Cohen BM, Baker JT, Brady RO, Ongur D, Shinn AK. Auditory hallucinations across the psychosis spectrum: Evidence of dysconnectivity involving cerebellar and temporal lobe regions. Neuroimage Clin. 2021;32:102893. doi: 10.1016/j.nicl.2021.102893. Epub 2021 Nov 24.
PubMed 34911197Brady RO Jr, Beermann A, Nye M, Eack SM, Mesholam-Gately R, Keshavan MS, Lewandowski KE. Cerebellar-Cortical Connectivity Is Linked to Social Cognition Trans-Diagnostically. Front Psychiatry. 2020 Nov 4;11:573002. doi: 10.3389/fpsyt.2020.573002. eCollection 2020.
PubMed 33329111Ward HB, Brady RO Jr, Halko MA. Bridging the Gap: Strategies to Make Psychiatric Neuroimaging Clinically Relevant. Harv Rev Psychiatry. 2021 May-Jun 01;29(3):185-187. doi: 10.1097/HRP.0000000000000295.
PubMed 33882534Halko MA, Farzan F, Eldaief MC, Schmahmann JD, Pascual-Leone A. Intermittent theta-burst stimulation of the lateral cerebellum increases functional connectivity of the default network. J Neurosci. 2014 Sep 3;34(36):12049-56. doi: 10.1523/JNEUROSCI.1776-14.2014.
PubMed 25186750Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.
PubMed 15664172
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Empirical Validation of a Cerebellar-cortical Hallucination Circuit
- ClinicalTrials.gov ID
- NCT05343598
- Acronym / sponsor ID
- 2021P002459
- Conditions
- Schizophrenia, Schizo Affective Disorder
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, National Institute of Mental Health (NIMH)
- Study start
- 13 Oct 2021 (actual)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 25 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study how hallucinations work in schizophrenia.
TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study the investigators will be stimulating the brain to learn more about how TMS might improve these symptoms of schizophrenia.
Detailed description
This study tests the hypothesis that hallucinations in schizophrenia are mediated by network pathophysiology, and that network pathophysiology can be quantified by the functional connectivity of a cerebellar-thalamo-cortical circuit. To accomplish this, participants will be recruited who are diagnosed with schizophrenia or schizoaffective disorder who experience auditory hallucinations.
Participants will undergo an initial screening session to complete informed consent and undergo baseline assessments of schizophrenia symptom severity. These assessments include reporter-based measures such as the Positive and Negative Syndrome Scale (PANSS).
Participants will then undergo an MRI scan that includes structural and resting-state functional magnetic resonance imaging (rsfMRI). These rsfMRI imagines will be used to isolate individual resting state networks for targeting of rTMS modulation.
Participants will then undergo five days of twice daily rTMS sessions.
One week after the last rTMS session, participants will undergo follow-up MRI imaging and the same study assessments.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active cerebellum rTMS | Active comparator | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)Cerebellar targeted iTBS, twice daily, one week. |
| Sham cerebellum rTMS | Sham comparator | Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)Cerebellar targeted sham iTBS, twice daily, one week. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Diagnosis of schizophrenia or schizoaffective disorder
Key exclusion criteria (9 listed)
- substance use disorder in past 3 months
- ambidexterity
- contraindications for TMS or MRI including :
- history of neurological disorder
- history of head trauma resulting in loss of consciousness
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 |
|---|---|---|
| Repetitive Transcranial Magnetic Stimulation (rTMS)Also: iTBSrTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry. The rTMS pulses will be delivered in a pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz every 10s for 600 total pulses. | Device | Active cerebellum rTMS |
| Sham Repetitive Transcranial Magnetic Stimulation (rTMS)Also: iTBSrTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry. The rTMS pulses will be delivered in a pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz every 10s for 600 total pulses. Sham is achieved by using a coil with a magnetic shield preventing magnetic field from reaching the head. | Device | Sham cerebellum rTMS |
Primary outcome
functional connectivity
Time frame: baseline, 1 week after TMS
change in functional connectivity of a putative cerebellar-thalamic-cortical hallucination circuit (cerebellum to thalamus) will be assessed before and after (1 week followup) TMS stimulation.
Positive and Negative Syndrome Scale (PANSS)
Time frame: baseline
The PANSS is clinical rating scale of symptom severity . Each descriptor is rated on a 7 point scale from 1=(absence of any symptom) to 7=(extremely severe symptoms).
Scale for the Assessment of Positive Symptoms (SAPS)
Time frame: baseline
The SAPS is clinical rating scale of symptom severity . Each descriptor is rated on a 5 point scale from 1=(absence of any symptom) to 5=(extremely severe symptoms).
Auditory Hallucination Rating Scale (AHRS) Scale (AHRS)
Time frame: baseline
The AHRS is a 7-item clinical rating scale used to assess auditory hallucinations.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2026.
- Background: PubMed 30696271Brady RO Jr, Gonsalvez I, Lee I, Ongur D, Seidman LJ, Schmahmann JD, Eack SM, Keshavan MS, Pascual-Leone A, Halko MA. Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia. Am J Psychiatry. 2019 Jul 1;176(7):512-520. doi: 10.1176/appi.ajp.2018.18040429. Epub 2019 Jan 30.
- Background: PubMed 34653740Basavaraju R, Ithal D, Thanki MV, Ramalingaiah AH, Thirthalli J, Reddy RP, Brady RO Jr, Halko MA, Bolo NR, Keshavan MS, Pascual-Leone A, Mehta UM, Kesavan M. Intermittent theta burst stimulation of cerebellar vermis enhances fronto-cerebellar resting state functional connectivity in schizophrenia with predominant negative symptoms: A randomized controlled trial. Schizophr Res. 2021 Dec;238:108-120. doi: 10.1016/j.schres.2021.10.005. Epub 2021 Oct 12.
- Background: PubMed 32648915Nawaz U, Lee I, Beermann A, Eack S, Keshavan M, Brady R. Individual Variation in Functional Brain Network Topography is Linked to Schizophrenia Symptomatology. Schizophr Bull. 2021 Jan 23;47(1):180-188. doi: 10.1093/schbul/sbaa088.
- Background: PubMed 34911197Hwang M, Roh YS, Talero J, Cohen BM, Baker JT, Brady RO, Ongur D, Shinn AK. Auditory hallucinations across the psychosis spectrum: Evidence of dysconnectivity involving cerebellar and temporal lobe regions. Neuroimage Clin. 2021;32:102893. doi: 10.1016/j.nicl.2021.102893. Epub 2021 Nov 24.
- Background: PubMed 33329111Brady RO Jr, Beermann A, Nye M, Eack SM, Mesholam-Gately R, Keshavan MS, Lewandowski KE. Cerebellar-Cortical Connectivity Is Linked to Social Cognition Trans-Diagnostically. Front Psychiatry. 2020 Nov 4;11:573002. doi: 10.3389/fpsyt.2020.573002. eCollection 2020.
- Background: PubMed 33882534Ward HB, Brady RO Jr, Halko MA. Bridging the Gap: Strategies to Make Psychiatric Neuroimaging Clinically Relevant. Harv Rev Psychiatry. 2021 May-Jun 01;29(3):185-187. doi: 10.1097/HRP.0000000000000295.
- Background: PubMed 25186750Halko MA, Farzan F, Eldaief MC, Schmahmann JD, Pascual-Leone A. Intermittent theta-burst stimulation of the lateral cerebellum increases functional connectivity of the default network. J Neurosci. 2014 Sep 3;34(36):12049-56. doi: 10.1523/JNEUROSCI.1776-14.2014.
- Background: PubMed 15664172Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.
- Individual participant dataSharing planned: No. deidentified participant data will be shared with NIMH Data Repository (NDA).
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
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.
Mark Halko, PhD contact
Mark Halko, PhD principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation (rTMS) in people with Schizophrenia and Schizo Affective Disorder, run by Mclean Hospital at 1 site 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 1 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mark Halko, PhD (mhalko@mclean.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
functional connectivity (time frame: baseline, 1 week after TMS). The study lists 4 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 NCT05343598, which also lists 8 linked publications.
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 22 Jan 2026.