Ignite Creation Date:
2024-05-06 @ 1:06 PM
Last Modification Date:
2024-10-26 @ 1:09 PM
Study NCT ID:
NCT03932136
Status:
RECRUITING
Last Update Posted:
2023-10-31
First Post:
2019-04-23
Brief Title:
Decreasing Risk of Psychosis by Sulforaphane DROPS Trial
Sponsor:
Shanghai Jiao Tong University School of Medicine
Organization:
Shanghai Jiao Tong University School of Medicine
Study Overview
Official Title:
Decreasing Risk of Psychosis by Sulforaphane Study Protocol for a Randomized Double-blind Placebo-controlled Clinical Multicenter Trial DROPS Trial
Status:
RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
SettingThis 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 criteriaThe 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 andor 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 andor 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 andor 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 exitdiscontinuation 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 testWe 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 SIPSSOPS 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
SettingThis 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 criteriaThe 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 andor 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 andor 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 andor 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 exitdiscontinuation 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 testWe 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 SIPSSOPS 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None