Alternative Stimulation Mode and Location for Auditory Hallucination Neuromodulation Treatment

July 30, 2026 updated by: Xiaoming Du, The University of Texas Health Science Center, Houston
The purpose of the study is to test the hypothesis that functionally navigated repetitive TMS stimulations to the prefrontal cortex (PFC) modulate aberrant cortical electrical activities at PFC circuitry. The TMS location of the PFC site will be individually localized by the symptom-related functional connectivity between PFC and symptom related areas (such as the auditory and language processing cortex). The investigators predict that such modulation will correct abnormal activities in patients with schizophrenia, reduce symptoms, especially auditory hallucination, and improve working memory/sustained attention performance.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Neuroimaging studies suggest that aberrant activities at specific brain regions such as sensory areas and language-related areas are related to psychosis symptoms including auditory and visual hallucination, delusion, and thought disorders. Transcranial magnetic stimulation (TMS) provides a non-invasive means for altering brain electrical neural activity. TMS has been approved by FDA for treatment of depression. Other applications have not been approved but it has been used in a wide range of clinical research especially in neurology and psychiatry. Among psychotic symptoms, there are preliminary significant improvement in treatments of auditory hallucination using TMS with small samples, but those treatments are not robust in larger samples. The high inter-subject variability limits the efficacy of TMS treatment in schizophrenia patients. The investigators aim to develop a TMS treatment method with a fMRI-defined treatment target area, where the TMS target is individually identified to maximize the TMS effects. The identification method uses both the anatomical character and its functional relationship with auditory hallucination and other psychosis symptoms. If the current target-identification successfully identified effective TMS target individually, the treatment efficacy will be significant improved and more patients will benefit from TMS treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
140

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas Health Science Center at Houston
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 62 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male and female ages between ages 18-50 years
  • Ability to give written informed consent (age 18 or above)
  • Diagnosed with schizophrenia-spectrum disorder and Evaluation to Sign Consent (ESC) above 10.
  • Is currently under the care of a licensed primary care provider or mental healthcare provider (e.g., psychiatrist, psychologist, nurse practitioner, licensed clinical social worker).
  • Have auditory hallucinations despite treated by two or more antipsychotics including one atypical antipsychotic medication.
  • Agrees to: (a) provide written permission, as requested, to allow any and all forms of communication between the investigators and study staff and any health care provider who currently provides and/or has provided service to the subject within two years of study enrollment; and (b) provide the names and verifiable contact information (name, email and mailing address, mobile and land-line phone number, as applicable) of at least two reliable persons ≥ age 22, who reside within a 30-minute drive of the subject's residence, and whom the research staff is at liberty to contact, as deemed necessary, for the duration of study participation.

Exclusion Criteria:

  • Persons with a first-degree relative with inherited epilepsy, seizure disorder, or seizures or persons who answer "yes" to any of the parts (A. - G.) of Question 3 of an epilepsy screening questionnaire.
  • Taking > 400 mg clozapine/day and not on anti-seizure medication(s) with sufficient dose.
  • Failed TMS screening questionnaire.
  • Significant alcohol or other drug use (substance abuse within 1 month or substance dependence history within 6 months and having substance usage within 1 month) other than nicotine or marijuana dependence
  • Any major medical illnesses that may affect normal brain functioning. Examples of these conditions include, but not limited to, stroke, CNS infection or tumor, other significant brain neurological conditions.
  • Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed.
  • History of head injury with loss of consciousness over 10 minutes; history of brain surgery
  • Cannot refrain from using alcohol and/or marijuana 24 hours or more prior to experiments.
  • Woman who is pregnant (child-bearing potential but not on contraceptive and missing menstrual period; or by self-report; or by positive pregnancy test) or has had unprotected sexual intercourse without birth control in the last 4 weeks.
  • Moderate-High Risk of suicide according to the Columbia - Suicide Severity Rating Scale (C-SSRS) Screen Version - Recent (i.e. answers YES to Question 3 and NO to Question 6 (Moderate risk); or answers YES to Questions 4, 5, or 6 (High risk) or in the clinical judgement of the investigator or the study psychiatrist.
  • In the medical opinion of the investigator, subjects with the following circumstances or conditions which can increase the risk of seizures may be excluded: sleep deprivation; major depressive disorder comorbid with dementia, underweight status; concurrent use of cephalosporins and antiarrhythmics (particularly propranolol); metabolic abnormalities (hyponatremia, hypocalcemia, hypomagnesemia, hypoglycemia, hyperglycemia, renal failure/uremia, liver failure); raised blood concentrations of proconvulsant medications due to reduced clearance (e.g. secondary to initiation of antibiotics for treatment of infections); alcohol withdrawal; use of stimulants, such as cocaine or MDMA; use of immunosuppressive therapy with cyclosporine, tacrolimus and other agents that can cause the posterior reversible leukoencephalopathy syndrome; dialysis; systemic infection, and fever itself.
  • History (or family history) of deep vein thrombosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Active rTMS stimulation
Device: Active rTMS stimulation
Participants will receive two rTMS sessions in each treatment visit for up to 22 visits within about 6 weeks. There is a 30-minute rest between the two rTMS sessions.
Sham Comparator: Sham rTMS stimulation
Device: Sham rTMS stimulation
Participants will receive two sham rTMS sessions in each treatment visit for up to 22 visits within about 6 weeks. There is a 30-minute rest between the two sham rTMS sessions.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Brain connectivity as indicated by resting state functional connectivity value as assessed by functional magnetic resonance imaging (fMRI)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Functional magnetic resonance imaging (fMRI) is used to evaluate the brain activities that are corresponding to the treatment effect on auditory hallucination.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Electrophysiological responses as indicated by mismatch negativity amplitudes from electroencephalography recording (EEG)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Electroencephalogram (EEG) is used to evaluate the brain electrical activities that are corresponding to the treatment effect on auditory hallucination.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Electrophysiological responses as indicated by steady-state auditory evoked potentials from electroencephalography recording (EEG)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Electroencephalogram (EEG) is used to evaluate the brain electrical activities that are corresponding to the treatment effect on auditory hallucination.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Auditory hallucinations as assessed by Psychotic Symptom Rating Scale (PSYRATS)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Total score ranges from 0 to 44, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Negative symptoms as assessed by Brief Negative Symptom Scale (BNSS)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Total score ranges from 0 to 90, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Cognitive insight as assessed by the Beck Cognitive Insight Scale (BCIS)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Total score ranges from 15 to 60, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Depression as assessed by the Beck Depression Inventory measures the severity of depression
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Total score ranges from 0 to 63, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Depression as assessed by the Calgary Depression Scale for Schizophrenia (CDSS)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Total score ranges from 0 to 27, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Perception as assessed by the Perception State and Trait Scales (State score)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
The Perception State and Trait Scale measures subtle auditory and visual anomalies. State total score ranges from 0 to 48, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Perception as assessed by the Perception State and Trait Scales (Trait score)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
The Perception State and Trait Scale measures subtle auditory and visual anomalies. Trait total score ranges from 0 to 48, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Delusion as assessed by the Peters Delusions Inventory (yes/no score)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
The Peters Delusions Inventory measures subtle delusional tendencies. Yes/No total score ranges from 0 to 21, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Delusion as assessed by the Peters Delusions Inventory (distress score)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
The Peters Delusions Inventory measures subtle delusional tendencies. Distress total score ranges from 0 to 105, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Delusion as assessed by the Peters Delusions Inventory (pre-occupation score)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
The Peters Delusions Inventory measures subtle delusional tendencies. Pre-occupation total score ranges from 0 to 105, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
Delusion as assessed by the Peters Delusions Inventory (conviction score)
Time Frame: baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)
The Peters Delusions Inventory measures subtle delusional tendencies. Conviction total score ranges from 0 to 105, with a lower score indicating a better outcome.
baseline, intermittent (before or at the beginning of treatment visit 11, about 2 weeks after baseline), end of acute treatment (after treatment visit 20, about 4 weeks after baseline)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The University of Texas Health Science Center, Houston

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Mental Health (NIMH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Xiaoming Du, PhD, The University of Texas Health Science Center, Houston

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 28, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 23, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 27, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HSC-MS-24-0336
  • R61MH128390 (U.S. NIH Grant/Contract)

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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