Cognitive Impairment, Schizophrenia, Treatment Resistant Schizophrenia
Conditions
Keywords
tDCS, aerobic exercise, cognitive function, treatment-resistant schizophrenia
Brief summary
Cognitive impairment is a major determinant of disability in schizophrenia. Aerobic exercise improves global cognition in schizophrenia, particularly working memory and attention/vigilance. Transcranial direct current stimulation (tDCS) targeting frontal regions has shown promise for cognitive deficits, including working memory improvements in some studies. This randomized 2×2 factorial trial will test the independent and combined effects of supervised aerobic exercise and prefrontal tDCS on cognition in treatment resistant schizophrenia, measured using the MATRICS Consensus Cognitive Battery (MCCB).
Detailed description
This is an individually randomized, sham controlled (tDCS), assessor blinded 2×2 factorial clinical trial comparing: (1) aerobic exercise vs stretching/education control and (2) active vs sham prefrontal tDCS. The factorial design enables estimation of the main effects of exercise and tDCS and their interaction (synergy/antagonism) in one trial. Participants with treatment resistant schizophrenia (TRS) will complete 18 sessions over 6 weeks (3 sessions/week). Each session includes tDCS (active or sham) during the physical activity condition (aerobic exercise or stretching/education) to standardize timing and contact. Evidence suggests exercise associated cognitive gains relate to intervention dose and supervision. Noninvasive brain stimulation outcomes may vary with stimulation dose parameters, supporting a standardized protocol. Cognition will be assessed using the MCCB, which evaluates seven cognitive domains relevant to schizophrenia and yields an Overall Composite T score. The primary endpoint is Week 6 (end of intervention), with durability assessed at 3 months post intervention (Week 18).
Interventions
BEHAVIORALAerobic Exercise
* Dose: 18 sessions over 6 weeks (3/week) * Session duration: 45-60 minutes including warm up/cool down * Intensity: Moderate (target 60-75% HRR or RPE 12-15) * Mode: Aerobic dance * Delivery: Supervised by qualified staff; HR/RPE logged each session * Rationale: Exercise improves global cognition and domains such as working memory and attention/vigilance in schizophrenia; supervision/dose relate to effect size.
BEHAVIORALStretching/Education Control
* Dose: 18 sessions over 6 weeks (3/week) * Session duration: 45-60 minutes * Intensity: Low (HR \<40% HRR; RPE \<10) * Components: Stretching + standardized health education modules * Purpose: Attention matched control to reduce contact/expectancy bias in non pharmacological trials.
DEVICEActive tDCS
* Montage: Anode F3 (left DLPFC), cathode Fp2 (right supraorbital) * Intensity: 2.0 mA * Duration: 20 minutes (30 s ramp up/down) * Schedule: 18 sessions (one per visit) * Rationale: Frontal tDCS protocols have shown promise for cognitive deficits and working memory in schizophrenia
DEVICESham tDCS
• Same montage; ramp up then off (device standard sham) to mimic cutaneous sensations.
Sponsors
Kit Wa Chan
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* DSM 5 schizophrenia-spectrum disorders * Treatment resistant schizophrenia: inadequate response to ≥2 antipsychotics of adequate dose/duration * Clinically stable ≥4 weeks * Able to provide informed consent
Exclusion criteria
* Neurological disorder (e.g., epilepsy, stroke) or significant head injury * Implanted electronic devices / contraindications to tDCS; scalp lesions at electrode sites * Medical contraindications to moderate aerobic exercise * Substance dependence within 3 months (except nicotine) * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MCCB Overall Composite T score change from baseline (Week 0) to end of intervention (Week 6). | 6 weeks | MCCB provides standardized domain and composite T scores for schizophrenia cognition research. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MCCB Working Memory Domain change (LNS + WMS III Spatial Span domain T score) baseline to Week 6. | 6 weeks | Working memory is responsive to exercise in schizophrenia meta-analysis and frequently targeted in frontal tDCS studies. |
| MCCB Attention/Vigilance Domain change (CPT IP domain T score) baseline to Week 6. | 6 weeks | Attention/vigilance improves with exercise in schizophrenia meta analysis; attention demanding performance may improve in some tDCS protocols. |
| Changes of negative symptoms measured with SANS from baseline to week 6 | 6 weeks | Studies have shown effectiveness of exercise and tDCS on improvement of negative symptoms in patients with schizophrenia |
| Durability of changes of negative symptoms relative to baseline and week 6 | 18 weeks | Evaluates the persistence of the improvement of negative symptoms |
Countries
Hong Kong
Contacts
CONTACTKit Wa Chan, MD
CONTACTYifan Chen, PhD
PRINCIPAL_INVESTIGATORKit Wa Chan, MD
The University of Hong Kong
Outcome results
None listed