NCT05343598

Brief 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. In this study the investigators will be stimulating the brain to learn more about how TMS might improve these symptoms of schizophrenia.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
68

participants targeted

Target at P50-P75 for not_applicable schizophrenia

Timeline
5mo left

Started Oct 2021

Longer than P75 for not_applicable schizophrenia

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress90%
Oct 2021Oct 2026

Study Start

First participant enrolled

October 13, 2021

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

April 13, 2022

Completed
12 days until next milestone

First Posted

Study publicly available on registry

April 25, 2022

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2026

Last Updated

January 22, 2026

Status Verified

January 1, 2026

Enrollment Period

5.1 years

First QC Date

April 13, 2022

Last Update Submit

January 21, 2026

Conditions

SchizophreniaSchizo Affective Disorder

Outcome Measures

Primary Outcomes (4)

  • 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.

    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).

    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).

    baseline

  • Auditory Hallucination Rating Scale (AHRS) Scale (AHRS)

    The AHRS is a 7-item clinical rating scale used to assess auditory hallucinations.

    baseline

Study Arms (2)

Active cerebellum rTMS

ACTIVE COMPARATOR

Cerebellar targeted iTBS, twice daily, one week.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Sham cerebellum rTMS

SHAM COMPARATOR

Cerebellar targeted sham iTBS, twice daily, one week.

Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS)DEVICE

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.

Also known as: iTBS
Active cerebellum rTMS
Sham Repetitive Transcranial Magnetic Stimulation (rTMS)DEVICE

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.

Also known as: iTBS
Sham cerebellum rTMS

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Diagnosis of schizophrenia or schizoaffective disorder

You may not qualify if:

  • 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
  • metal in brain or skull
  • implanted devices such as a pacemaker, medication pump, nerve stimulator or ventriculoperitoneal shunt
  • claustrophobic in MRI

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

RECRUITING

Related Publications (8)

  • 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.

    PMID: 30696271BACKGROUND

  • Basavaraju 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.

    PMID: 34653740BACKGROUND

  • Nawaz 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.

    PMID: 32648915BACKGROUND

  • Hwang 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.

    PMID: 34911197BACKGROUND

  • Brady 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.

    PMID: 33329111BACKGROUND

  • Ward 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.

    PMID: 33882534BACKGROUND

  • Halko 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.

    PMID: 25186750BACKGROUND

  • Huang 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.

    PMID: 15664172BACKGROUND

MeSH Terms

Conditions

SchizophreniaPsychotic Disorders

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Officials

  • Mark Halko, PhD

    Mclean Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark Halko, PhD

CONTACT

mhalko@mclean.harvard.edu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
The subjects, care providers, investigators and outcome assessors will all be blinded as to the randomization sequence, and thus will be blinded as to sham vs active TMS status. Blinding codes are used to determine which side of an active/passive Magpro coil (cool B65 A/P, Magventure A/S, Denmark) is used for stimulation.
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Psychiatry

Study Record Dates

First Submitted

April 13, 2022

First Posted

April 25, 2022

Study Start

October 13, 2021

Primary Completion (Estimated)

October 31, 2026

Study Completion (Estimated)

October 31, 2026

Last Updated

January 22, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

deidentified participant data will be shared with NIMH Data Repository (NDA).

Locations

US(1)