Schizophrenia, Schizoaffective Disorder
Conditions
Keywords
Schizophrenia, Schizoaffective Disorder, Sulforaphane, Sulforaphane supplement
Brief summary
The purpose of this study is to determine if taking a sulforaphane nutraceutical versus a placebo will reduce symptoms of schizophrenia when used in addition to standard antipsychotic medications.
Interventions
DRUGSulforaphane Nutraceutical
Sulforaphane Nutraceutical 6 tablets by mouth daily
Identical-appearing Placebo 6 tablets by mouth daily
Sponsors
Sheppard Pratt Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Capacity for written informed consent * Age 18-65 years, inclusive * Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnosis of schizophrenia or schizoaffective disorder as determined by the Structured Clinical Interview for DSM-5 Disorders (SCID-5) * Currently an outpatient at time of screening * Residual psychotic symptoms of at least moderate severity as evidenced by a Positive and Negative Syndrome Scale (PANSS) total score of 60 or higher AND one or more of the following: one or more PANSS positive symptom scores of 4 or higher; OR containing at least three positive or negative items with scores of 3 or higher at the screening visit * Receiving antipsychotic medication for at least 8 weeks prior to enrolling in the study with no antipsychotic medication changes within the previous 21 days from visit 2 (week 0) * Conformance to PORT Treatment Recommendation about Maintenance Antipsychotic Medication Dose * Proficient in the English language * Participated previously in one of our screening studies
Exclusion criteria
* Any clinically significant or unstable medical disorder as determined by the principal investigator and/or the study physician (e.g., HIV infection or other immunodeficiency condition (such as receiving chemotherapy), uncontrolled diabetes, congestive heart failure) * DSM-5 diagnosis of intellectual disability or comparable diagnoses determined by previous versions of the DSM * DSM-5 diagnosis of a moderate or severe substance use disorder, except for caffeine or tobacco, within the last three months prior to the screening visit. If the patient has a positive drug toxicity screen at the time of visit 1 (screening), further evaluation by the investigator will be done of the substance use to determine eligibility. * Any current use of a broccoli supplement (e.g., Avmacol® or other health food broccoli supplement) * Participated in any investigational drug trial in the past 30 days prior to the screening visit * Pregnant, planning to become pregnant, or breastfeeding during the study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Positive and Negative Syndrome Scale (PANSS) Score From the Start to the End of the Double-blind Treatment Phase | 16 weeks (week 2 to week 18) | The Positive and Negative Syndrome Scale (PANSS) measures psychiatric symptomatology, especially related to psychosis. The complete PANSS contains ratings for 30 symptoms, including 7 positive symptoms, 7 negative symptoms, and 16 general psychiatric symptoms. The severity of each symptom is rated on a scale ranging from 1 (minimal) to 7 (extreme); higher scores indicate increased symptomatology. Total PANSS scores include scores from all categories and range from 30 to 210 units on a scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in C-Reactive Protein From the Start to the End of the Study | 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported) | — |
| Change in Pentraxin-3 From the Start to the End of the Study | 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported) | — |
| Change in Anti-Saccharomyces Cerevisiae IgA Class Antibodies From the Start to the End of the Study | 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported) | — |
| Change in MATRICS Consensus Cognitive Battery (MCCB) Overall Composite Scores From the Start to the End of the Study | 18 weeks (week 0 to week 18) | The MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) is a standardized battery of 10 tests that measure 7 domains of cognitive performance: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Overall composite t-scores are calculated using scores from all subtests. A t-score of 50 (10) is the mean (standard deviation) of the relevant reference population. Higher values indicate better performance. |
| Change in Tumor Necrosis Factor - Alpha From the Start to the End of the Study | 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported) | — |
| Change in Interferon Gamma From the Start to the End of the Study | 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported) | — |
| Change in Interleukin-6 From the Start to the End of the Study | 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported) | — |
Countries
United States
Participant flow
Recruitment details
We enrolled n=64 participants drawn from rehabilitation and treatment programs in Central Maryland. Dates of recruitment: February 2017 - June 2019.
Pre-assignment details
We used a 2 week single-blind placebo phase for all participants prior to randomization. This placebo run-in was followed by the 16 week double-blind treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| Sulforaphane Nutraceutical Sulforaphane nutraceutical 6 tablets by mouth daily for 16 weeks | 32 |
| Identical-appearing Placebo Identical-appearing placebo 6 tablets by mouth daily for 16 weeks | 32 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Treatment Phase (16 Weeks) | Lost to Follow-up | 1 | 0 |
| Double-Blind Treatment Phase (16 Weeks) | Protocol Violation | 0 | 1 |
| Double-Blind Treatment Phase (16 Weeks) | Relocation | 1 | 0 |
| Double-Blind Treatment Phase (16 Weeks) | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Sulforaphane Nutraceutical | Identical-appearing Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 32 Participants | 64 Participants |
| Age, Continuous | 42.7 years STANDARD_DEVIATION 12.3 | 45.8 years STANDARD_DEVIATION 11.7 | 44.2 years STANDARD_DEVIATION 12 |
| Race/Ethnicity, Customized African American | 14 participants | 16 participants | 30 participants |
| Race/Ethnicity, Customized Caucasian | 18 participants | 16 participants | 34 participants |
| Region of Enrollment United States | 32 participants | 32 participants | 64 participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 24 Participants | 25 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 28 / 32 | 20 / 32 |
| serious Total, serious adverse events | 2 / 32 | 5 / 32 |
Outcome results
Primary
Change in Positive and Negative Syndrome Scale (PANSS) Score From the Start to the End of the Double-blind Treatment Phase
The Positive and Negative Syndrome Scale (PANSS) measures psychiatric symptomatology, especially related to psychosis. The complete PANSS contains ratings for 30 symptoms, including 7 positive symptoms, 7 negative symptoms, and 16 general psychiatric symptoms. The severity of each symptom is rated on a scale ranging from 1 (minimal) to 7 (extreme); higher scores indicate increased symptomatology. Total PANSS scores include scores from all categories and range from 30 to 210 units on a scale.
Time frame: 16 weeks (week 2 to week 18)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane Nutraceutical | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Start to the End of the Double-blind Treatment Phase | Wk 2 (Begin Treatment) PANSS Total Score | 81.0 score on a scale | Standard Deviation 12.2 |
| Sulforaphane Nutraceutical | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Start to the End of the Double-blind Treatment Phase | Wk 18 (End Treatment) PANSS Total Score | 81.7 score on a scale | Standard Deviation 13.3 |
| Identical-appearing Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Start to the End of the Double-blind Treatment Phase | Wk 2 (Begin Treatment) PANSS Total Score | 81.5 score on a scale | Standard Deviation 13 |
| Identical-appearing Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Start to the End of the Double-blind Treatment Phase | Wk 18 (End Treatment) PANSS Total Score | 79.7 score on a scale | Standard Deviation 14.6 |
Secondary
Change in Anti-Saccharomyces Cerevisiae IgA Class Antibodies From the Start to the End of the Study
Time frame: 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane Nutraceutical | Change in Anti-Saccharomyces Cerevisiae IgA Class Antibodies From the Start to the End of the Study | ASCA IGA (Wk 0, Baseline) | 0.195 units/ml | Standard Deviation 0.222 |
| Sulforaphane Nutraceutical | Change in Anti-Saccharomyces Cerevisiae IgA Class Antibodies From the Start to the End of the Study | ASCA IGA (Wk 18, End Treatment) | 0.226 units/ml | Standard Deviation 0.277 |
| Identical-appearing Placebo | Change in Anti-Saccharomyces Cerevisiae IgA Class Antibodies From the Start to the End of the Study | ASCA IGA (Wk 0, Baseline) | 0.168 units/ml | Standard Deviation 0.163 |
| Identical-appearing Placebo | Change in Anti-Saccharomyces Cerevisiae IgA Class Antibodies From the Start to the End of the Study | ASCA IGA (Wk 18, End Treatment) | 0.176 units/ml | Standard Deviation 0.184 |
Secondary
Change in C-Reactive Protein From the Start to the End of the Study
Time frame: 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane Nutraceutical | Change in C-Reactive Protein From the Start to the End of the Study | CRP (Wk 0, Baseline) | 10402.8 ng/ml | Standard Deviation 13488.2 |
| Sulforaphane Nutraceutical | Change in C-Reactive Protein From the Start to the End of the Study | CRP (Wk 18, End Treatment) | 10198.5 ng/ml | Standard Deviation 12110.9 |
| Identical-appearing Placebo | Change in C-Reactive Protein From the Start to the End of the Study | CRP (Wk 0, Baseline) | 8969.7 ng/ml | Standard Deviation 9021.6 |
| Identical-appearing Placebo | Change in C-Reactive Protein From the Start to the End of the Study | CRP (Wk 18, End Treatment) | 10224.5 ng/ml | Standard Deviation 13654 |
Secondary
Change in Interferon Gamma From the Start to the End of the Study
Time frame: 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane Nutraceutical | Change in Interferon Gamma From the Start to the End of the Study | IFN-g (Wk 0, Baseline) | 0.514 pg/m | Standard Deviation 0.432 |
| Sulforaphane Nutraceutical | Change in Interferon Gamma From the Start to the End of the Study | IFN-g (Wk 18, End Treatment) | 0.478 pg/m | Standard Deviation 0.335 |
| Identical-appearing Placebo | Change in Interferon Gamma From the Start to the End of the Study | IFN-g (Wk 0, Baseline) | 0.456 pg/m | Standard Deviation 0.172 |
| Identical-appearing Placebo | Change in Interferon Gamma From the Start to the End of the Study | IFN-g (Wk 18, End Treatment) | 0.526 pg/m | Standard Deviation 0.222 |
Secondary
Change in Interleukin-6 From the Start to the End of the Study
Time frame: 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane Nutraceutical | Change in Interleukin-6 From the Start to the End of the Study | IL-6 (Wk 0, Baseline) | 0.623 pg/m | Standard Deviation 0.247 |
| Sulforaphane Nutraceutical | Change in Interleukin-6 From the Start to the End of the Study | IL-6 (Wk 18, End Treatment) | 0.694 pg/m | Standard Deviation 0.288 |
| Identical-appearing Placebo | Change in Interleukin-6 From the Start to the End of the Study | IL-6 (Wk 0, Baseline) | 0.704 pg/m | Standard Deviation 0.478 |
| Identical-appearing Placebo | Change in Interleukin-6 From the Start to the End of the Study | IL-6 (Wk 18, End Treatment) | 0.673 pg/m | Standard Deviation 0.357 |
Secondary
Change in MATRICS Consensus Cognitive Battery (MCCB) Overall Composite Scores From the Start to the End of the Study
The MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) is a standardized battery of 10 tests that measure 7 domains of cognitive performance: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Overall composite t-scores are calculated using scores from all subtests. A t-score of 50 (10) is the mean (standard deviation) of the relevant reference population. Higher values indicate better performance.
Time frame: 18 weeks (week 0 to week 18)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane Nutraceutical | Change in MATRICS Consensus Cognitive Battery (MCCB) Overall Composite Scores From the Start to the End of the Study | Wk 0 (Baseline) MCCB Score | 25.0 t scores | Standard Deviation 12 |
| Sulforaphane Nutraceutical | Change in MATRICS Consensus Cognitive Battery (MCCB) Overall Composite Scores From the Start to the End of the Study | Wk 18 (End Treatment) MCCB Score | 26.8 t scores | Standard Deviation 12.6 |
| Identical-appearing Placebo | Change in MATRICS Consensus Cognitive Battery (MCCB) Overall Composite Scores From the Start to the End of the Study | Wk 0 (Baseline) MCCB Score | 19.5 t scores | Standard Deviation 13.4 |
| Identical-appearing Placebo | Change in MATRICS Consensus Cognitive Battery (MCCB) Overall Composite Scores From the Start to the End of the Study | Wk 18 (End Treatment) MCCB Score | 22.8 t scores | Standard Deviation 13.6 |
Secondary
Change in Pentraxin-3 From the Start to the End of the Study
Time frame: 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane Nutraceutical | Change in Pentraxin-3 From the Start to the End of the Study | Pentraxin(Wk 0, Baseline) | 0.414 ng/ml | Standard Deviation 0.534 |
| Sulforaphane Nutraceutical | Change in Pentraxin-3 From the Start to the End of the Study | Pentraxin (Wk 18, End Treatment) | 0.394 ng/ml | Standard Deviation 0.569 |
| Identical-appearing Placebo | Change in Pentraxin-3 From the Start to the End of the Study | Pentraxin(Wk 0, Baseline) | 0.461 ng/ml | Standard Deviation 0.603 |
| Identical-appearing Placebo | Change in Pentraxin-3 From the Start to the End of the Study | Pentraxin (Wk 18, End Treatment) | 0.558 ng/ml | Standard Deviation 0.695 |
Secondary
Change in Tumor Necrosis Factor - Alpha From the Start to the End of the Study
Time frame: 18 weeks (assessed at weeks 0, 10, and 18; weeks 0 and 18 reported)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sulforaphane Nutraceutical | Change in Tumor Necrosis Factor - Alpha From the Start to the End of the Study | TNF-a (Wk 0, Baseline) | 0.668 pg/m | Standard Deviation 0.393 |
| Sulforaphane Nutraceutical | Change in Tumor Necrosis Factor - Alpha From the Start to the End of the Study | TNF-a (Wk 18, End Treatment) | 0.638 pg/m | Standard Deviation 0.362 |
| Identical-appearing Placebo | Change in Tumor Necrosis Factor - Alpha From the Start to the End of the Study | TNF-a (Wk 18, End Treatment) | 0.520 pg/m | Standard Deviation 0.263 |
| Identical-appearing Placebo | Change in Tumor Necrosis Factor - Alpha From the Start to the End of the Study | TNF-a (Wk 0, Baseline) | 0.538 pg/m | Standard Deviation 0.211 |