Decreasing Risk of Psychosis by Sulforaphane: Study Protocol for a Randomized, Double-blind, Placebo-controlled, Clinical Multicenter Trial (DROPS Trial)

Study design: This study is designed as a randomized, double-blind, placebo-controlled, clinical multi-centre trial. Its main objective is to evaluate the efficacy of SFN vs placebo in decreasing risk and conversion rate of psychosis in CHR population. A total of 300 CHR subjects will be recruited at eight research centres. All participants will be provided withan explanation about the study, and informed consent will be obtained from each participant before participation. The study duration includes an intervention with SFN or placebo for 52 consecutive weeks, and additional 1-year follow-up. The primary outcome is conversion rate of psychosis at the end of follow-up (104 weeks). The secondary outcomes mainly include conversion rate of psychosis at the end of intervention (52 weeks), the severity and the duration of prodromal symptoms, predictive risk of psychosis conversion, neurocognitive functioning and biomarkers of inflammation, oxidative stress and metabolism in peripheral blood. Safety outcomes include side-effects, serious adverse events, laboratory tests, which will be obtained from all participants.

Setting:This study involves eight research centres in China include Shanghai Mental Health Center, Shanghai Xuhui District Mental Health Center, Shanghai Pudong Nanhui Mental Health Center, Suzhou Guangji Hospital, Second Xiangya Hospital of Central South University, Guangzhou Huiai Hospital, Tianjin Anding Hospital, and the First Affiliated Hospital of Zhengzhou University. Shanghai Mental Health Center is the leading centre. Before the trial, standardized training in interview and rating will be provided to all centres equally.

CHR identification: CHR subjects will be identified in the course of face-to-face interviews using the structured interview for prodromal syndromes (SIPS) (Miller et al., 2002; Miller et al., 2003). CHR subjects meet the criteria of prodromal syndromes (COPS) for the attenuated positive symptom syndrome (APSS), brief intermittent psychotic syndrome (BIPS), or genetic risk and deterioration syndrome (GRDS) according to the SIPS. CHR diagnosis will be made by a panel of senior psychiatrists. Severity of CHR subjects' prodromal symptoms will be assessed using the scale of prodromal symptoms (SOPS) (Miller et al., 1999) based on SIPS. In addition, the Positive and Negative Syndrome Scale (PANSS) will be used for rating the severity of psychotic symptoms.

Inclusion criteria:The inclusion criteria of this study are as follows: (a) Subjects meet the criteria of CHR according to SIPS; (b) Subjects will have no history of being medicated with either antipsychotics or mood stabilizers at their first study visit; (c) Age, within the range of 15 to 45 years; (d) Patients and/or their legal guardians for those younger than 18 year old, can understand and sign informed consent, and agree to take the study interventions and complete all visits and examinations.

Exclusion criteria: The exclusion criteria of this study are as follows: (a) A history of schizophrenia or any other psychotic disorders; (b) Severe physical diseases (ie, cardiac and neurologic diseases, brain trauma, liver and kidney diseases, haematopoietic system and immune system dysfunction), or cancer, or other serious complicated diseases; (c) IQ < 70 is assessed by Wechsler Adult Intelligence Scale-Revised in China, or a specific of developmental delay or intellectual disability; (d) Abnormal laboratory test results with clinical significance which will affect the safety of participants as determined by the investigator; (e) A past and/or current abuse of alcohol, amphetamine or any other psychostimulants; (f) Suicidal ideation, plan, or suicidal behaviour in the last 3 months; (g) Clinically significant allergic reaction to broccoli; (h) Pregnancy or preparing for pregnancy, and/or lactation; (i) Participation in another clinical trial within the last 30 days. (j) Other conditions that make the candidate subject unsuitable for this study as determined by the principal investigators (eg, aggressive behaviour, safety concerns, difficulty to complete the follow-up, etc.).