Alternative Stimulation Mode and Location for Auditory Hallucination Neuromodulation Treatment

NCT ID: NCT02916810

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-01
• Study Completion Date: 2029-07-01

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.

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.

Conditions

Schizophrenia and Related Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active rTMS stimulation

Group Type: ACTIVE_COMPARATOR

Active rTMS stimulation

Intervention Type: 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.

Sham rTMS stimulation

Group Type: SHAM_COMPARATOR

Sham rTMS stimulation

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Xiaoming Du

Assistant Professsor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiaoming Du, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Xiaoming Du, PhD

Role: CONTACT

Xiaoming.Du@uth.tmc.edu

(713) 486-2700

Facility Contacts

Xiaoming Du, PhD

Role: primary

Xiaoming.Du@uth.tmc.edu

713-486-2700

Other Identifiers

R61MH128390

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC-MS-24-0336

Identifier Type: -

Identifier Source: org_study_id