Cerebellar Modulation of Cognition in Psychosis

The goal of this clinical trial is to learn about cognition in psychotic disorders (schizophrenia, bipolar disorder, and schizoaffective disorder). The main question it aims to answer is: Can we use magnetic stimulation to change processing speed (how quickly people can solve challenging tasks).

Participants will be asked to perform cognitive tasks (problem-solving) and undergo brain scans before and after transcranial magnetic stimulation (TMS). TMS is a way to non-invasively change brain activity. Forms of TMS are FDA-approved to treat depression and obsessive compulsive disorder. In this study, we will use a different form of TMS to temporarily change brain activity to observe how that changes speed in problem-solving.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizoaffective Disorder; Psychosis; Bipolar Disorder I
• Intervention / Treatment: Device: intermittant theta burst stimulation (iTBS); Device: continuous theta burst stimulation (cTBS); Device: sham rTMS

Detailed Description

Psychotic disorders including schizophrenia, bipolar disorder, and related illnesses are severe, debilitating, and often fatal. Cognitive impairments in psychosis are among the leading predictors of disability and poor quality of life; despite this, there are no first-line interventions to target these symptoms.

This trial will test the hypothesis that cognitive performance in these disorders is modifiable and specifically that it can be modified non-invasively. Transcranial magnetic stimulation (TMS) is a neuromodulation technique that utilizes magnets to alter brain activity non-invasively. TMS has received FDA approval as a therapeutic intervention for multiple psychiatric disorders. In this study, we will use different forms of TMS to modulate a specific brain circuit and we will measure the outcomes of this circuit manipulation. These outcomes include performance on cognitive tests and also changes to the circuit itself that we can measure using magnetic resonance imaging (MRI).

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Recruiting
      • McLean Hospital
      • Contact: Madelaine Nye, B.S.; Phone Number: 617-855-2370; Email: mnye@mclean.harvard.edu
      • Principal Investigator: Kathryn E Lewandowski, Ph.D.
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Madelaine Nye; Phone Number: 617-632-7956; Email: mnye@bidmc.harvard.edu
      • Principal Investigator: Roscoe O Brady, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 18-55 years
• Diagnosis of a psychotic disorder (i.e. schizophrenia or schizoaffective disorder or bipolar disorder type I)
• Must be able to read, speak and understand English
• Must be judged by study staff to be capable of completing the study procedures
• Participants will be in stable outpatient treatment with no recent (within the past 30 days) hospitalizations or changes in their medication regimens.

Exclusion Criteria:

• Diagnostic and Statistical Manual 5 diagnosis of moderate substance use disorder within the past month

• Conditions that might result in increased risks of side effects or complications from rTMS or MRI, including:

  • Intracranial pathology from a known genetic disorder (e.g., Neurofibromatosis 1, tuberous sclerosis) or from acquired neurologic disease (e.g. stroke, tumor), cerebral palsy, history of severe head injury, or significant dysmorphology;
  • History of fainting spells of unknown or undetermined etiology that might constitute seizures
  • History of multiple seizures or diagnosis of epilepsy
  • Any progressive (e.g., neurodegenerative) neurological disorder such as multiple sclerosis or Parkinson's disease
  • Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
  • Metal implants (excluding dental fillings) unless cleared by the responsible covering MD (i.e. MRI compatible joint replacement)
  • Pacemaker
  • Implanted medication pump
  • Vagal nerve stimulator
  • Deep brain stimulator or transcutaneous electric nerve stimulation unit
  • Ventriculo-peritoneal shunt
  • Signs of increased intracranial pressure
  • Intracranial lesion
  • History of head injury resulting in prolonged loss of consciousness (>15minutes) or neurological sequelae
  • Pregnancy: All participants capable of becoming pregnant will be required to have a pregnancy test; any participant who is pregnant will not be enrolled in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intermittent theta burst stimulation (iTBS); Participants complete MRI scanning and cognitive testing followed by rTMS (iTBS pattern) followed by repeat cognitive testing and MRI scanning	Device: intermittant theta burst stimulation (iTBS); iTBS consists of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses.
Active Comparator: continuous theta burst stimulation (cTBS); Participants complete MRI scanning and cognitive testing followed by rTMS (cTBS pattern) followed by repeat cognitive testing and MRI scanning	Device: continuous theta burst stimulation (cTBS); cTBS consists of 3 pulses at 50 Hz repeated at 5 Hz (every 200ms) continuously for a total of 600 pulses
Sham Comparator: sham rTMS; Participants complete MRI scanning and cognitive testing followed by sham rTMS followed by repeat cognitive testing and MRI scanning	Device: sham rTMS; sham rTMS does not deliver a significant change in magnetic field strength

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BACS Symbol Coding test	The BACS Symbol coding test is a test of information processing speed	eight minutes before TMS and one minute after TMS on each of the three TMS visit days
BACS Digit Sequence test	The BACS digit sequence test is a test of working memory performance	five minutes before TMS and four minutes after TMS on each of the three TMS visit days
functional Magnetic Resonance Imaging	resting-state (task free) functional connectivity	fifteen minutes before TMS and nine minutes after TMS on each of the three TMS visit days

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Collaborators: Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2024
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: October 19, 2023
• First Submitted That Met QC Criteria: October 24, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: 2023P002474

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes