Transcranial Magnetic Stimulation (TMS) for Negative Symptoms in Schizophrenia Spectrum Disorders

Official title

TMS for Negative Symptoms in Schizophrenia Spectrum Disorders

Overview

The purpose of this study is to determine if repetitive transcranial magnetic stimulation (rTMS) applied to angular gyrus (AG) will improve negative symptoms and/or other psychosis symptoms in schizophrenia spectrum disorders (SSD) patients compared with prefrontal cortex (PFC) or sham.

Interventions

• Device TMS
  A wire coil is held on the scalp. Brief electrical currents are passed through the coil and create one or more magnetic pulses that stimulate the brain. For each TMS session, bursts of 3 pulses at 50 Hz are repeated at 5 Hz as a train for 2seconds. The inter-train interval is 8 seconds. There are 20 trains lasting 192 seconds (600pulses) per session. The intensity of TMS stimulations is set to 80-120% of resting motor threshold(RMT).
• Device sham
  Participants will receive total of 2 s of theta burst sham stimulation (TBS) trains repeated every 10 s for a total of 20 cycles (600 pulses). No actual magnetic stimulation will occur, still participant hears the TMS sound and a skin sensation

Primary outcome measures

• Change in blood-brain barrier (BBB) water exchange rate at AG obtained from MRI scan [Time frame: baseline (before treatment visit 1), midpoint (after treatment visit 10; about 2 weeks from baseline), and end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]

Secondary outcome measures (12)

• Change in Negative symptoms as assessed by the Brief Negative Symptom Scale (BNSS) [Time frame: at baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Positive symptoms as assessed by the Positive and Negative Syndrome Scale (PANSS) [Time frame: at baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Cognitive function as assessed by Brief Assessment of Cognition in Schizophrenia (BACS): Symbol Coding [Time frame: t baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Working memory as assessed by the Number Span test [Time frame: t baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Working memory as assessed by the Wechsler Memory Scale-Third Edition (WMS-III): Spatial Span [Time frame: t baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Cognitive function as assessed by the Category Fluency Test: Animal naming (Fluency) [Time frame: t baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Cognitive function as assessed by the Rey-Osterrieth Complex Figure Test [Time frame: t baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Cognitive function as assessed by the Bell Lysaker Emotion Recognition Task [Time frame: t baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Cognitive function as assessed by the Hinting Task [Time frame: t baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Depression as assessed by the Patient Health Questionnaire (PHQ-9) [Time frame: t baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Depression as assessed by the Calgary Depression Scale [Time frame: t baseline, after treatment visit 10 (about 2 weeks from baseline), and at the end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]
• Change in Resting state functional connectivity between AG and PFC assessed by functional MRI (fMRI) [Time frame: at baseline (before treatment visit 1), midpoint (after treatment visit 10; about 2 weeks from baseline), and end of acute treatment (after treatment visit 20; about 4 weeks from baseline)]

Eligibility criteria

Inclusion criteria

• Ability to give written informed consent
• 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 negative symptoms as determined by BNSS score of 20 or more.
• Agrees to 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

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 dependence within the recent months) or positive urine toxicology screen for substance not prescribed 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, Central nervous System (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
• 0 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 2 and NO to Question 6 (Moderate risk); or answers YES to Questions 3 (Moderate risk), 4, 5, or 6 (High risk) or in the clinical judgement of the investigator or the study psychiatrist.
• History (or family history) of deep vein thrombosis.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 1 center

• The University of Texas Health Science Center at Houston — Houston

Identifiers

NCT: NCT07290738 · HSC-MS-25-0694

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗