Clinical trial NCT06961916: Enhancing Brain Connectivity in Schizophrenia Through Neuromodulation (Study 2)
Official title: Enhancing Brain Connectivity in Schizophrenia Through Neuromodulation (Study 2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia
Keywords: Transcranial magnetic stimulation
schizophrenia
white matter
connectivity
myelination
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2025-05-08
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients with schizophrenia spectrum disorder (SSD) will be exposed to active repetitive transcranial magnetic stimulation (rTMS) from H coil combined with cognitive training for improving white matter integrity.

Detailed description: Schizophrenia is a severe mental illness that affects about 1% of the population but a major source of disability. Information processing between brain regions occurs due to transfer of electrical impulses among them. This process is determined by the existing neuronal/fiber connections, which may be altered and or modified in the presence of neuronal stimulation or cognitive intervention. The frontal lobe information flow is critical for higher cognitive functions, thought processes, and proper emotional and behavioral responses. Improving the myelination in the frontal lobe may increase cognitive functions and reduce risks to develop symptoms of schizophrenia. The investigators propose that increasing electrical signaling in the frontal white matter in patients with schizophrenia may also enhance myelination and improve the white matter integrity.

The patients with schizophrenia will receive active repetitive transcranial magnetic stimulation (rTMS) treatment combined with cognitive training. The rTMS with H coil is FDA-cleared for short-term smoking cessation in the general population. The efficacy of its combination with cognitive training in myelination modulation has not been evaluated.

Eligibility criteria: Inclusion Criteria:

1. Male and female ages between ages 18-60 years
2. Ability to give written informed consent (age 18 or above)
3. Diagnosed with schizophrenia-spectrum disorder and Evaluation to Sign Consent (ESC) above 10.

Exclusion Criteria:

1. Inability to sign informed consent.
2. Any history of seizures.
3. Any acute and unstable major medical illnesses that may affect normal brain functioning. Examples of these conditions include, but not limited to, recent stroke, seizure, history of significant head trauma, CNS infection or tumor, other significant brain neurological conditions (As this is a study of medical comorbidity, most medical conditions, once stable, are not exclusion criteria).
4. Taking \> 400 mg clozapine/day and not on anti-seizure medication(s) with sufficient dose.
5. Failed TMS screening questionnaire.
6. 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.
7. A history of thrombosis, family history of thrombosis, or medical conditions that may lead to a hypercoagulable state (increased chance to develop blood clots)
8. Woman who is pregnant (child-bearing potential but not on contraceptive and missing menstrual period; or by self-report; or by positive urine pregnancy test).
9. History of head injury with loss of consciousness over 10 minutes; history of brain surgery
10. Cannot refrain from using alcohol and/or marijuana 24 hours or more prior to experiments.
11. Students and employees currently involved with our lab (lab employees and personnel will be excluded from the study to avoid possible coercion or possible appearance of coercion, or chance of breach of privacy and confidentiality).
12. For MRI, unable to undergo MRI scanning due to metallic devices or objects (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips, or other implanted metal parts) or claustrophobic to the scanner.

Primary outcomes:
measure: Brain microstructural integrity as indicated by white matter fractional anisotropy (FA) values as assessed by magnetic resonance imaging (MRI)
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Brain connectivity as indicated by resting-state functional connectivity (rsFC) values as assessed by functional MRI (fMRI)
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
Secondary outcomes:
measure: Electrophysiological response as indicated by mismatch negativity as assessed by electroencephalography (EEG)
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Electrophysiological response as indicated by steady-state auditory evoked responses from electroencephalography recording (EEG)
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Cognitive insight as assessed by the Beck Cognitive Insight Scale
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Depression as assessed by the Depression State and Trait Scale (DST) - state
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Depression as assessed by the Depression State and Trait Scale (DST) - trait
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Depression as assessed by the Calgary Depression Scale
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Depression as assessed by the Beck Depression Inventory
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Perception as assessed by the Perception State and Trait Scale - state
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Perception as assessed by the Perception State and Trait Scale - trait
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Delusion as assessed by the 21-item Peters Delusion Inventory (PDI-21)
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Emotion regulation as assessed by the Profile of Mood States (POMS)
timeFrame: day 1 after baseline, day 2 after baseline, day 3 after baseline, day 4 after baseline, day 5 after baseline, day 9 after baseline, day 10 after baseline,
measure: Hallucination as assessed by the Revised Hallucinations Scale (RHS)
timeFrame: day 1 after baseline, day 2 after baseline, day 3 after baseline, day 4 after baseline, day 5 after baseline, day 9 after baseline, day 10 after baseline
measure: Cognitive function as assessed by the Letter-Number Span subscale of the MATRICS consensus cognitive battery (MCCB)
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
measure: Cognitive function as assessed by the Spatial Span subscale of the MATRICS consensus cognitive battery (MCCB)
timeFrame: baseline, visit 6 (about 1 week after baseline), visit 10 (about 2 weeks after baseline)
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center, Houston
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Xiaoming Du, PhD
role: PRINCIPAL_INVESTIGATOR
References: