Schizophrenia Disorder
Conditions
Brief summary
The goal of this randomized, double-blind, placebo-controlled clinical trial with an open-label extension is to evaluate whether sulforaphane can improve negative symptoms and cognitive impairment, and to explore its underlying mechanisms in patients with schizophrenia (aged 12-45 years, both sexes, stable on antipsychotic medication). The study duration includes 12 weeks of double-blind treatment followed by a 12-week open-label extension. In the randomized controlled double-blind phase, a total of 60 participants will be randomized 1:1 to receive either six oral tablets (411 μmol GR) of sulforaphane (SFN group, n = 30) or placebo (placebo group, n = 30) for 12 weeks. In the open-label phase, participants will choose whether to continue taking the drugs originally assigned. The primary outcome is the change in PANSS and BNSS scores during the randomized double-blind phase. Secondary outcomes include changes in brain MRI measures, as well as changes in MCCB, CGI-SI, CGI-GI, PSP, SNS, and SAFTEE scores during the randomized double-blind phase; and changes in PANSS, BNSS, and MCCB scores during the open-label phase.SAFTEE scale, serious adverse event record and blood test will be used for safety monitoring.
Interventions
DIETARY_SUPPLEMENTPlacebo
Participants take 6 tablets of matching placebo daily for the first 3 months (randomized double-blind phase). During the subsequent 3-month open-label extension phase, those who choose to continue their original assigned medication also take 6 tablets of matching placebo per day, i.e., six placebo tablets daily. Both active and placebo tablets are manufactured uniformly by Shenzhen Fushan Biotech Co., Ltd. (China), with identical appearance and similar smell and taste.
DIETARY_SUPPLEMENTSulforaphane
Participants take 6 tablets of sulforaphane daily for the first 3 months (randomized double-blind phase). During the subsequent 3-month open-label extension phase, those who choose to continue their original assigned medication also take 6 tablets of sulforaphane per day, equivalent to a dosage of six active tablets (411 μmol GR). The sulforaphane-producing dietary supplement, ZHIYINGUOSU, is provided at no cost by Shenzhen Fushan Biotech Co., Ltd. (China).
Sponsors
Second Xiangya Hospital of Central South University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
An interventional, randomized controlled clinical trial with an open-label extension study
Eligibility
Sex/Gender
ALL
Age
12 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of schizophrenia according to DSM-5 criteria. 2. First-episode or illness duration ≤ 10 years, but currently in a non-acute phase of schizophrenia. 3. Negative symptoms present for ≥ 6 months prior to study entry. Patients must be outpatients or hospitalized for social reasons rather than symptom exacerbation. 4. PANSS negative subscale (7 items) total score ≥ 20; at least one negative item score \> 3; no change \> 3 points between screening and baseline. PANSS positive subscale items related to agitation (P4 excitement, P6 suspiciousness/persecution, P7 hostility, G8 uncooperativeness, G14 poor impulse control) each ≤ 4. 5. Currently taking ≤ 2 antipsychotic medications. 6. Antipsychotic regimen remains unchanged during the study period. 7. No anticipated relocation, transportation difficulties, or access problems that would interfere with study participation. 8. Able to understand and comply with study procedures, complete all required tests and examinations, communicate well with the investigator, and voluntarily provide written informed consent
Exclusion criteria
1. Psychiatric symptoms attributable to any other DSM-5 diagnosis besides schizophrenia. 2. History of substance dependence, or psychotic symptoms caused by other medical conditions. 3. Calgary Depression Scale for Schizophrenia (CDSS) total score \> 6. 4. Barnes Akathisia Rating Scale (BARS) score indicating at least moderate akathisia. 5. Current or past major physical illness, neurological disorder, or traumatic brain injury affecting brain structure/function. 6. Suicidal attempt or current suicidal ideation. 7. Currently receiving antidepressants, mood stabilizers; or use of rTMS, MECT, or systematic psychotherapy within 3 months or for the current episode. 8. Current use of medications that may affect cognitive function, such as Ginkgo biloba extract, minocycline, selegiline. 9. Presence of hepatic or renal insufficiency, severe gastrointestinal, respiratory, endocrine, or hematologic disorders, or disorders of absorption or metabolism. 10. Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the Positive and Negative Syndrome Scale (PANSS) negative subscale score | Baseline to 6 and 12 weeks | PANSS negative subscale assesses severity of negative symptoms (score range 7-49, higher = worse). Change scores are calculated as the score at each time point (6 and 12 weeks) minus the baseline score. A negative change at either time point indicates improvement. |
| Change from baseline in Brief Negative Symptom Scale (BNSS) score | Baseline to 6 and 12 weeks | The BNSS measures negative symptom severity (total score 0-78, higher = worse). Change from baseline = score at week minus baseline score (calculated separately for week 6 and week 12). A negative change at either time point indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in MATRICS Consensus Cognitive Battery (MCCB) score | Baseline to 12 weeks | The MCCB assesses seven cognitive domains. Positive change indicates cognitive improvement. |
| Brain imaging changes | Baseline to 12 weeks | Evaluation of brain imaging changes from baseline at week 12. The scanning protocol includes structural imaging, functional imaging, diffusion imaging, myelin imaging, and magnetic resonance spectroscopy imaging, to systematically evaluate brain structure, functional connectivity, white matter microstructure, myelin integrity, and neurometabolic profiles in patients with schizophrenia. |
| Change in serum biomarker levels | Baseline to 12 weeks | Evaluation of peripheral blood biomarkers of inflammation, oxidative stress and metabolism |
| Change in PANSS negative subscale score (open-label extension) | Week 12 to 24 | Evaluation of the change from week 12 in the negative symptom subscale of PANSS at week 24. Change = score at 24 weeks minus score at week 12. Negative change indicates further improvement during extension. |
| Change in Brief Negative Symptom Scale (BNSS) (open-label extension) | Week 12 to 24 | BNSS total score (0-78, higher=worse). Change = 24-week score minus week-12 score. Negative change indicates further improvement during extension. |
| Change in the composite score of MATRICS Consensus Cognitive Battery (MCCB) (open-label extension) | Week 12 to 24 | Evaluation of the score and change from week 12 in MCCB composite score at week 24. Change = 24-week score minus week-12 score. Positive change indicates further improvement during extension |
| Change in serum biomarker levels (open-label extension) | Week 12 to 24 | Serum biomarker concentrations. Change = level at 24 weeks minus level at week 12. |
| Clinical Global Impression - Severity of Illness (CGI-SI) score | Baseline to 6 and 12 weeks | CGI-SI rates illness severity on a 7-point scale (1=normal, 7=extremely ill). Change = score at week minus baseline score (separately for week 6 and week 12). Negative change indicates improvement. |
| Clinical Global Impression - Global Improvement (CGI-GI) score | Week 6 and week 12 | The CGI-GI rates overall change on a 7-point scale (1=very much improved, 4=no change, 7=very much worse). The score at each time point (6 and 12 weeks) directly reflects improvement since baseline; lower scores mean greater improvement. |
| Change in Self-rating Negative Symptom Scale (SNS) score | Baseline to 6 and 12 weeks | The SNS is a self-reported scale completed by the patient to assess the severity of negative symptoms. Each item is scored on a 3-point scale (0=strongly disagree, 1=slightly agree, 2=completely agree), yielding a total score ranging from 0 to 40, with higher scores indicating more severe negative symptoms. Change scores are calculated as the score at each time point (6 and 12 weeks) minus the baseline score. A negative change at either time point indicates symptomatic improvement. |
| Change in Personal and Social Performance (PSP) total score | Baseline to 6 and 12 weeks | The PSP total score ranges 1-100 (higher = better personal and social functioning). Change = week score minus baseline score (separately for week 6 and week 12). Positive change means functional improvement. |
| Change in Barnes Akathisia Rating Scale (BARS) total score | Baseline to 6 and 12 weeks | The BARS measures akathisia severity (total score 0-14, higher = worse). Change = week score minus baseline score (separately for week 6 and week 12). Negative change indicates reduced akathisia. |
| Change in Systematic Assessment for Treatment Emergent Events (SAFTEE) total score | Baseline to 6 and 12 weeks | The SAFTEE total score reflects adverse event burden (higher score = greater burden). Change = week score minus baseline score (separately for week 6 and week 12). Negative change means reduction in adverse events. |
| Clinical Global Impression - Severity of Illness (CGI-SI) score (open-label extension) | Week 24 | CGI-SI rates illness severity on a 7-point scale (1=normal, 7=extremely ill). |
| Clinical Global Impression - Global Improvement (CGI-GI) score (open-label extension) | Week 24 | The CGI-GI rates overall change on a 7-point scale (1=very much improved, 4=no change, 7=very much worse). The score at 24 weeks directly reflects improvement since baseline; lower scores mean greater improvement. |
| Change in Self-rating Negative Symptom Scale (SNS) score (open-label extension) | Week 12 to 24 | The SNS is a patient-reported outcome measuring negative symptom severity using a 3-point scale per item (0=strongly disagree, 1=slightly agree, 2=completely agree), with a total score range of 0 to 40 (higher = worse). Change is calculated as the score at 24 weeks minus the score at week 12. A negative change indicates further improvement in negative symptoms during the extension phase. |
| Change in Personal and Social Performance (PSP) total score (open-label extension) | Week 12 to 24 | The PSP total score ranges 1-100 (higher = better personal and social functioning). Change = week 24 score minus week 12 score. Positive change means functional improvement. |
| Change in BARS total score (open-label extension) | Week 12 to 24 | The BARS measures akathisia severity (total score 0-14, higher = worse). Change = week score minus baseline score (separately for week 6 and week 12). Negative change indicates reduced akathisia. |
| Change in Systematic Assessment for Treatment Emergent Events (SAFTEE) total score (open-label extension) | Week 12 to 24 | he SAFTEE total score reflects adverse event burden (higher score = greater burden). Change = week 24 score minus week 12 score. Negative change means reduction in adverse events. |
Countries
China
Contacts
CONTACTJing Huang, Prof.
Outcome results
None listed