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NCT Number: NCT07404319

Effectiveness of Exercise Alone and tDCS+Exercise on Cognitive Function Improvement in Patients With Treatment Resistant Schizophrenia

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).

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Key information

Conditions

Schizophrenia Cognition Disorders Cognitive Dysfunction Cognitive Impairment Mental Disorders Neurocognitive Disorders Schizophrenia Spectrum and Other Psychotic Disorders Schizophrenia, Treatment-Resistant Treatment Resistant Schizophrenia

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Aerobic Exercise

Behavioral
  • 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.

Stretching/Education Control

Behavioral
  • 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.

active tDCS

Device
  • 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

Sham tDCS

Device
  • Same montage; ramp up then off (device standard sham) to mimic cutaneous sensations.

Primary outcomes

  1. MCCB Overall Composite T score change from baseline (Week 0) to end of intervention (Week 6).

    Time frame: 6 weeks

    MCCB provides standardized domain and composite T scores for schizophrenia cognition research.

Secondary outcomes

  1. MCCB Working Memory Domain change (LNS + WMS III Spatial Span domain T score) baseline to Week 6.

    Time frame: 6 weeks

    Working memory is responsive to exercise in schizophrenia meta-analysis and frequently targeted in frontal tDCS studies.

  2. MCCB Attention/Vigilance Domain change (CPT IP domain T score) baseline to Week 6.

    Time frame: 6 weeks

    Attention/vigilance improves with exercise in schizophrenia meta analysis; attention demanding performance may improve in some tDCS protocols.

  3. Changes of negative symptoms measured with SANS from baseline to week 6

    Time frame: 6 weeks

    Studies have shown effectiveness of exercise and tDCS on improvement of negative symptoms in patients with schizophrenia

  4. Durability of changes of negative symptoms relative to baseline and week 6

    Time frame: 18 weeks

    Evaluates the persistence of the improvement of negative symptoms

Other outcomes

  1. Durability: MCCB Overall Composite and key domains at 3 months post intervention (Week 18) relative to baseline and Week 6.

    Time frame: 18 weeks total

    Evaluates persistence of cognitive gains.

  2. Changes of social functioning measured with SOFAS from baseline to 18 weeks

    Time frame: 18 weeks

    Cognitive function and negative symptoms are closely related to social functioning. Improvement of these may contribute to the improvement of overall social functioning

  3. Durability: MCCB Overall Composite and key domains at 6 months post intervention (Week 24) relative to baseline and Week 6 and week 18

    Time frame: 24

    Evaluates persistence of cognitive gains

  4. Durability of improvement of negative symptoms at 6 months after intervention (week 24) relative to baseline, week 6 and week 18

    Time frame: 24 weeks

    Evaluates persistence of the improvement of negative symptoms

  5. Durability of the improvement of social functioning at 6 months post intervention (week 24) relative to baseline and week 18

    Time frame: 24 weeks

    Evaluates the persistence or even further improvement of the social functioning

Study contacts

Contact information is provided by the study sponsor or research team.

Kit Wa Chan, MD

CONTACT

[email protected]

852-22554489

Yifan Chen, PhD

CONTACT

[email protected]

852-22554486

Sponsors and collaborators

Lead sponsor

Kit Wa Chan

Other

Registry information

Official study title

Randomised Control Trial of Effectiveness of Exercise Alone and tDCS+Exercise on Cognitive Function Improvement in Patients With Treatment Resistant Schizophrenia

Acronym: TRACE

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Feb 11, 2026
Registry last updated
Feb 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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