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Decreasing Risk of Psychosis by Sulforaphane (DROPS Trial)

  • Clinicaltrials.gov identifier

    NCT03932136

  • Recruitment Status

    Recruiting

  • First Posted

    April 30, 2019

  • Last update posted

    June 17, 2020

Study Description

Brief summary:

This is a randomized, double-blind, placebo-controlled, multi-centre trial. A total of 300 CHR subjects will be identified in the course of face-to-face interviews using the Structured Interview for Prodromal Syndromes. All participants will be randomly allocated to SFN group (n = 150) or placebo group (n = 150). The study duration includes an intervention for 52 consecutive weeks, and additional 1-year follow-up. The primary outcome is 2-year conversion rate of psychosis. Secondary outcomes include 1-year conversion rate of psychosis, the severity and duration of prodromal symptoms, predictive risk of psychosis conversion, neurocognitive functioning and peripheral blood biomarkers of inflammation, oxidative stress and metabolism. Safety monitoring will be performed using scales for side effect, serious adverse events recording, and laboratory tests.

  • Condition or Disease:Clinical High Risk Syndrome of Psychosis
  • Intervention/Treatment: Dietary Supplement: Sulforaphane
    Combination Product: Placebo
  • Phase: Phase 3

Detailed Description

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.). The study will use the following exit/discontinuation criteria: (a) Voluntary discontinuation by the subject who is at any time free to discontinue his or her participation in the study, without prejudice to further assessment and treatment; (b) Severe non-compliance to protocol as judged by the investigator; (c) Subject meets criteria of transition to psychosis; (d) Subject meets exclusion criteria during the intervention (eg, physical diseases, pregnancy, etc.). Interventions: A total of 300 CHR subjects will be randomly allocated to SFN group (n = 150) or placebo group (n = 150). The intervention duration with SFN or placebo is 52 consecutive weeks. SFN will be delivered as its precursor GR along with a conversion enzyme, myrosinase, which converts GR to SFN in the body. The dosage is six active tablets (411 μmol GR) per day. ZHIYINGUOSU, SFN-producing dietary supplement, is provided at no cost by Shenzhen Fushan Biotech Co., Ltd. (China). The placebo group will be given six placebo tablets per day. Active and placebo tablets are manufactured uniformly with same appearance and similar smell and taste by Shenzhen Fushan Biotech Co., Ltd. (China). Patient compliance will be assessed using Brief Adherence Rating Scale (BARS). The BARS is a brief, pencil-paper, clinician-administered adherence assessment instrument. It consists of four items: three questions and an overall visual analogue rating scale to assess the proportion of doses taken by the patient in the past month (Byerly, Nakonezny, & Rush, 2008). Tablets counting will be conducted monthly for the whole intervention period. After intervention, a 1-year follow-up will be conducted. Temporary use of antipsychotics or anti-depressants is allowed in the whole trial based on the recommendation of the treating clinician, and the information of specific drugs, dosage, treatment period and rationale will be recorded. Safety: To evaluate the tolerability, we conducted a safety test in over 100 subjects, with the daily dosage is six active tablets. Apart from mild gastrointestinal discomfort, no significant safety or side-effect issues were found in this test.We also found that taking the tablets just after meal reduced the risk of gastrointestinal discomfort. Procedures in the proposed study allow the subject to increase the dosage gradually if the subject experiences significant gastrointestinal discomfort. If the subject experiences a serious adverse event his or her participation can be terminated. Outcomes: Clinical investigators will collect general information such as gender, age, height, weight, body mass index, demographics and medical history. In addition, vital signs and laboratory tests results will be obtained. These will include body temperature, arterial pulse, blood pressure, heart rate, complete blood cell count, blood electrolytes (K, Na, Cl) and liver and kidney function tests. The primary outcome is the 2-year conversion rate of psychosis at the end of follow-up (104 weeks). Psychosis conversion is operationally defined according to the criteria of POPS (presence of psychotic symptoms in SIPS/SOPS). Two are required: (a) at least one positive symptom is present at a psychotic level of intensity (rated at level '6' using SOPS); (b) any criterion symptom at sufficient frequency and duration or urgency: the symptom has occurred over a period of 1 month for at least 1 hour per day at a minimum average frequency of 4 days per week, or the symptom is seriously disorganizing or dangerous. The secondary outcomes include: (a) the 1-year conversion rate of psychosis at the end of intervention period (52 weeks); (b) scores of SOPS; (c) scores of PANSS; (d) the duration of psychotic symptoms; (e) Global Assessment of Functioning; (f) individual predictive risk of psychosis calculated by NAPLS-2 psychosis risk calculator (Carrion et al., 2016) and SHARP psychosis risk calculator (Zhang et al., 2019); (g) scores of MATRICS consensus cognitive battery (MCCB) (Kern et al., 2008; Nuechterlein et al., 2008); (h) the number of participants who receive antipsychotic treatment during the trial; (i) levels of peripheral blood biomarkers of inflammation, oxidative stress and metabolism. Others: (a) Serious adverse events; (b) side-effects of SFN and placebo will be assessed by Systematic Assessment For Treatment Emergent Events (SAFTEE) scale (Levine & Schooler, 1986); (c) Compliance to SFN or placebo assessed using BARS; (d) Usage of antidepressants or other medications; (e) plasma and urinary measures of GR metabolites.

Study Design

  • Study Type: Interventional
  • Estimated Enrollment: 300 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Primary Purpose: Prevention
  • Official Title: Decreasing Risk of Psychosis by Sulforaphane: Study Protocol for a Randomized, Double-blind, Placebo-controlled, Clinical Multicenter Trial (DROPS Trial)
  • Actual Study Start Date: July 2019
  • Estimated Primary Completion Date: December 2021
  • Estimated Study Completion Date: December 2021

Arms and interventions

Arm Intervention/treatment
Active Comparator: SFN group
The intervention duration with SFN tablet is 52 consecutive weeks. The dosage is six active tablets (411 μmol GR) per day.
Dietary Supplement: Sulforaphane
Sulforaphane (SFN) is a natural compound extracts from cruciferous vegetables, especially broccoli, with cytoprotective, anti-inflammatory, and antioxidant effects.
Placebo Comparator: Placebo group
The intervention duration with placebo tablet is 52 consecutive weeks. The placebo group will be given six placebo tablets per day.
Combination Product: Placebo
The placebo is safe, with no therapeutical effect, and has same appearance and similar smell and taste with active tablet.

Outcome Measures

  • Primary Outcome Measures: 1. 2-year conversion rate of psychosis [ Time Frame: 104 weeks ]
    The proportion of patients are diagnosed with psychosis in each group
  • Secondary Outcome Measures: 1. 1-year conversion rate of psychosis [ Time Frame: 52 weeks ]
    The proportion of patients is diagnosed with psychosis in each group
  • 2. Severity of prodromal symptoms [ Time Frame: 24 weeks, 52 weeks, 104 weeks ]
    CHR subject's severity of prodromal symptoms is assessed according to the Scale of Prodromal Symptoms (SOPS) based on the SIPS interview
  • 3. Severity of psychotic symptom [ Time Frame: 24 weeks, 52 weeks, 104 weeks ]
    CHR subject's severity of psychotic symptom is assessed according to the Positive and Negative Syndrome Scale (PANSS)
  • 4. Function [ Time Frame: 24 weeks, 52 weeks, 104 weeks ]
    CHR subject's overall function is assessed by Global Assessment of Functioning(GAF)
  • 5. Predictive risk of psychosis [ Time Frame: 24 weeks, 52 weeks, 104 weeks ]
    Predicted risk of psychosis by online psychosis risk calculator.
  • 6. Neurocognitive functioning [ Time Frame: 24 weeks, 52 weeks, 104 weeks ]
    The MATRICS consensus cognitive battery (MCCB). Original version of the MCCB comprises 10 standardized cognitive measures for seven cognitive domains: speed of processing, attention/vigilance, working memory (verbal and nonverbal), verbal learning, visual learning, reasoning and problem solving, and social cognition. The 7 domain scores and a composite score were used as variables of neurocognition.Our group has previously contributed to the Chinese norms for the MCCB scores of tests. The kappa values for test-retest reliability of the subtests of the Chinese version ranges from 0.73 to 0.94.
  • 7. Level of inflammation in subjects' peripheral blood [ Time Frame: 24 weeks, 52 weeks, 104 weeks ]
    Detecting expression levels of inflammation-related biomarkers in peripheral blood.
  • 8. Level of oxidative stress in subjects' peripheral blood [ Time Frame: 24 weeks, 52 weeks, 104 weeks ]
    Detecting expression levels of oxidative stress-related biomarkers in peripheral blood.
  • 9. Level of metabolism in subjects' peripheral blood [ Time Frame: 24 weeks, 52 weeks, 104 weeks ]
    Detecting expression levels of metabolism-related biomarkers in peripheral blood.
  • Other Outcome Measures: 1. Serious adverse events [ Time Frame: the whole process ]
    Serious adverse events
  • 2. Side-effects of SFN and placebo [ Time Frame: 52 weeks ]
    side-effects of SFN and placebo will be assessed by Systematic Assessment For Treatment Emergent Events (SAFTEE) scale
  • 3. Compliance [ Time Frame: 24 weeks ]
    Compliance to SFN or placebo assessed using Brief Adherence Rating Scale
  • 4. Number of CHR subjects who use antidepressants or other medications [ Time Frame: 52 weeks ]
    Usage of antidepressants or other medications
  • 5. Plasma and urinary measures of GR metabolites [ Time Frame: 24 weeks, 52 weeks, 104 weeks ]
    Plasma and urinary measures of GR metabolites

Eligibility Criteria

  • Ages Eligible for Study: 15 to 45 Years (Child, Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects meet the criteria of CHR according to the Structured Interview for Prodromal
Syndromes (SIPS);

2. Subjects will have no history of being medicated with either antipsychotics or mood
stabilizers at their first study visit;

3. Age, within the range of 15 to 45 years;

4. 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:

1. A history of schizophrenia or any other psychotic disorders;

2. 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;

3. IQ < 70 is assessed by Wechsler Adult Intelligence Scale-Revised in China, or a specific of developmental delay or intellectual disability; 4. Abnormal laboratory test results with clinical significance which will affect the safety of participants as determined by the investigator; 5. A past and/or current abuse of alcohol, amphetamine or any other psychostimulants; 6. Suicidal ideation, plan, or suicidal behaviour in the last 3 months; 7. Clinically significant allergic reaction to broccoli; 8. Pregnancy or preparing for pregnancy, and/or lactation; 9. Participation in another clinical trial within the last 30 days. 10. 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.).

Contacts and Locations

Contacts

Contact: Jijun Wang, PhD +8618616572179 jijunwang27@163.com

Contact: Zhixing Li, MD +8613026528898 iwisdomlee@163.com

Locations

China, Guangdong
Guangzhou Psychiatric Hospital
Guangzhou

China, Henan
the First Affiliated Hospital of Zhengzhou University
Zhengzhou

China, Hunan
Second Xiangya Hospital of Central South University
Changsha

China, Jiangsu
Suzhou Psychiatric Hospital
Suzhou

China, Shanghai
Shanghai Mental Health Center
Shanghai

China, Shanghai
Shanghai Xuhui District Mental Health Center
Shanghai

China, Shanghai
Shanghai Pudong Nanhui Mental Health Center
Shanghai

China, Tianjin
Tianjin Anding Hospital
Tianjin

Sponsors and Collaborators

Shanghai Jiao Tong University School of Medicine

Shanghai Xuhui District Mental Health Center

Shanghai Pudong Nanhui Mental Health Center

Suzhou Psychiatric Hospital

Second Xiangya Hospital of Central South University

Guangzhou Psychiatric Hospital

Shenzhen Fushan Biotech Co., Ltd.

Tianjin Anding Hospital

The First Affiliated Hospital of Zhengzhou University

Investigators

Study Director: Jijun Wang, PhD Shanghai Mental Health Center

Principal Investigator: Tianhong Zhang, PhD Shanghai Mental Health Center

Principal Investigator: Hua Jin, PhD University of California, San Diego

Principal Investigator: Xiaolong Li, PhD Shenzhen Fushan Biotech Co., Ltd.

More Information