Alternative Stimulation Mode and Location for Auditory Hallucination Neuromodulation Treatment

NCT02916810 | Recruiting DMC FDA Device

• 2 other identifiers: HSC-MS-24-0336R61MH128390
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia and Related Disorders

Keywords

transcranial magnetic stimulation; schizophrenia; MRI

Outcome Measures

Primary Outcomes (1)

• Brain connectivity as indicated by resting state functional connectivity value as assessed by functional magnetic resonance imaging (fMRI)

  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 Outcomes (13)

• Electrophysiological responses as indicated by mismatch negativity amplitudes from electroencephalography recording (EEG)

  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)

  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)

  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)

  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)

  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)

Study Arms (2)

Active rTMS stimulation

ACTIVE COMPARATOR

Device: Active rTMS stimulation

Sham rTMS stimulation

SHAM COMPARATOR

Device: Sham rTMS stimulation

Interventions

Active rTMS stimulation DEVICE

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.

Active rTMS stimulation

Sham rTMS stimulation DEVICE

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.

Sham rTMS stimulation

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Xiaoming Du, PhD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaoming Du, PhD

CONTACT

(713) 486-2700; Xiaoming.Du@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professsor

Study Record Dates

• First Submitted: June 28, 2016
• First Posted: September 27, 2016
• Study Start: February 1, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)