Mechanisms of Sulforaphane Supplementation in Alleviating Negative Symptoms and Cognitive Impairment in Schizophrenia

Overview

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 supplement Placebo
  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 supplement Sulforaphane
  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).

Primary outcome measures

• Change from baseline in the Positive and Negative Syndrome Scale (PANSS) negative subscale score [Time frame: Baseline to 6 and 12 weeks]
• Change from baseline in Brief Negative Symptom Scale (BNSS) score [Time frame: Baseline to 6 and 12 weeks]

Secondary outcome measures (12)

• Change from baseline in MATRICS Consensus Cognitive Battery (MCCB) score [Time frame: Baseline to 12 weeks]
• Brain imaging changes [Time frame: Baseline to 12 weeks]
• Change in serum biomarker levels [Time frame: Baseline to 12 weeks]
• Change in PANSS negative subscale score (open-label extension) [Time frame: Week 12 to 24]
• Change in Brief Negative Symptom Scale (BNSS) (open-label extension) [Time frame: Week 12 to 24]
• Change in the composite score of MATRICS Consensus Cognitive Battery (MCCB) (open-label extension) [Time frame: Week 12 to 24]
• Change in serum biomarker levels (open-label extension) [Time frame: Week 12 to 24]
• Clinical Global Impression - Severity of Illness (CGI-SI) score [Time frame: Baseline to 6 and 12 weeks]
• Clinical Global Impression - Global Improvement (CGI-GI) score [Time frame: Week 6 and week 12]
• Change in Self-rating Negative Symptom Scale (SNS) score [Time frame: Baseline to 6 and 12 weeks]
• Change in Personal and Social Performance (PSP) total score [Time frame: Baseline to 6 and 12 weeks]
• Change in Barnes Akathisia Rating Scale (BARS) total score [Time frame: Baseline to 6 and 12 weeks]

Eligibility criteria

Inclusion criteria

• Diagnosis of schizophrenia according to DSM-5 criteria.
• First-episode or illness duration ≤ 10 years, but currently in a non-acute phase of schizophrenia.
• Negative symptoms present for ≥ 6 months prior to study entry. Patients must be outpatients or hospitalized for social reasons rather than symptom exacerbation.
• 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.
• Currently taking ≤ 2 antipsychotic medications.
• Antipsychotic regimen remains unchanged during the study period.
• No anticipated relocation, transportation difficulties, or access problems that would interfere with study participation.
• 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

• Psychiatric symptoms attributable to any other DSM-5 diagnosis besides schizophrenia.
• History of substance dependence, or psychotic symptoms caused by other medical conditions.
• Calgary Depression Scale for Schizophrenia (CDSS) total score > 6.
• Barnes Akathisia Rating Scale (BARS) score indicating at least moderate akathisia.
• Current or past major physical illness, neurological disorder, or traumatic brain injury affecting brain structure/function.
• Suicidal attempt or current suicidal ideation.
• Currently receiving antidepressants, mood stabilizers; or use of rTMS, MECT, or systematic psychotherapy within 3 months or for the current episode.
• Current use of medications that may affect cognitive function, such as Ginkgo biloba extract, minocycline, selegiline.
• Presence of hepatic or renal insufficiency, severe gastrointestinal, respiratory, endocrine, or hematologic disorders, or disorders of absorption or metabolism.
• Pregnant or breastfeeding women.

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

China · 1 center

• Xiangya Second Hospital — Changsha

Identifiers

NCT: NCT07652866 · LYG20210114

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗