Trial Outcomes & Findings for Sulforaphane Treatment of Children With Autism Spectrum Disorder (ASD) (NCT NCT02561481)

NCT ID: NCT02561481

Last Updated: 2020-12-17

Results Overview

The Ohio Autism Clinical Impressions Scale-Severity (OACIS-S) rates severity of symptoms in 10 categories: general level of autism, social interaction, aberrant and repetitive behavior, verbal and nonverbal communication, hyperactivity, anxiety, sensory sensitivities and restricted and narrow interests. Each category is rated from 1 (normal) to 7 (most severe). The OACIS-S was a reference at follow up visits when the OACIS-Improvement was compared to the OACIS-S, from 1 to 7: 4 was no change; 3 to 1 minimal to marked improvement and 5 to 7 minimal to marked worsening. The numerical score of the OACIS-S is independent and unrelated quantitatively to the OACIS-I. For analysis, the OACIS-I general score and subscale values were recoded, in which 4 (no change) was recoded as 0; 3 to 1 were recoded as +1 to +3 to denote improvement, and 5 to 7 were recoded as -1 to -3 for worsening.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 60 participants
• Primary outcome timeframe: 7 weeks, 15 weeks, 22 weeks, 30 weeks, 36 weeks
• Results posted on: 2020-12-17

Participant Flow

Participant milestones

Measure	Sulforaphane Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
Pilot Trial STARTED	10	0
Pilot Trial COMPLETED	10	0
Pilot Trial NOT COMPLETED	0	0
Main Trial - Double Blind Phase STARTED	25	25
Main Trial - Double Blind Phase COMPLETED	22	23
Main Trial - Double Blind Phase NOT COMPLETED	3	2
Main Trial - Open Label Phase STARTED	45	0
Main Trial - Open Label Phase COMPLETED	32	0
Main Trial - Open Label Phase NOT COMPLETED	13	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sulforaphane Treatment of Children With Autism Spectrum Disorder (ASD)

Baseline characteristics by cohort

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description	Total n=45 Participants Total of all reporting groups
Age, Continuous	7.4 years STANDARD_DEVIATION 3.0 • n=5 Participants	7.0 years STANDARD_DEVIATION 2.5 • n=7 Participants	7.2 years STANDARD_DEVIATION 2.8 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Race/Ethnicity, Customized White	17 Participants n=5 Participants	15 Participants n=7 Participants	32 Participants n=5 Participants
Race/Ethnicity, Customized Other (asian, mixed, and unknown)	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	23 participants n=7 Participants	45 participants n=5 Participants

PRIMARY outcome

Timeframe: 7 weeks, 15 weeks, 22 weeks, 30 weeks, 36 weeks

Population: Patients started dropping out at subsequent visits so the number analyzed at latter visits is less

The Ohio Autism Clinical Impressions Scale-Severity (OACIS-S) rates severity of symptoms in 10 categories: general level of autism, social interaction, aberrant and repetitive behavior, verbal and nonverbal communication, hyperactivity, anxiety, sensory sensitivities and restricted and narrow interests. Each category is rated from 1 (normal) to 7 (most severe). The OACIS-S was a reference at follow up visits when the OACIS-Improvement was compared to the OACIS-S, from 1 to 7: 4 was no change; 3 to 1 minimal to marked improvement and 5 to 7 minimal to marked worsening. The numerical score of the OACIS-S is independent and unrelated quantitatively to the OACIS-I. For analysis, the OACIS-I general score and subscale values were recoded, in which 4 (no change) was recoded as 0; 3 to 1 were recoded as +1 to +3 to denote improvement, and 5 to 7 were recoded as -1 to -3 for worsening.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
Change in Ohio Autism Clinical Impressions Scale - Improvement (OACIS-I) Average Score From Baseline 7 weeks	0.28 score on a scale Standard Deviation 0.67	0.28 score on a scale Standard Deviation 0.57
Change in Ohio Autism Clinical Impressions Scale - Improvement (OACIS-I) Average Score From Baseline 15 weeks	0.28 score on a scale Standard Deviation 0.57	0.33 score on a scale Standard Deviation 0.69
Change in Ohio Autism Clinical Impressions Scale - Improvement (OACIS-I) Average Score From Baseline 22 weeks	0.47 score on a scale Standard Deviation 0.72	0.59 score on a scale Standard Deviation 0.71
Change in Ohio Autism Clinical Impressions Scale - Improvement (OACIS-I) Average Score From Baseline 30 weeks	0.47 score on a scale Standard Deviation 0.67	0.69 score on a scale Standard Deviation 0.77
Change in Ohio Autism Clinical Impressions Scale - Improvement (OACIS-I) Average Score From Baseline 36 weeks	0.29 score on a scale Standard Deviation 0.73	0.29 score on a scale Standard Deviation 0.61

SECONDARY outcome

Timeframe: 7 weeks, 15 weeks, 22 weeks, 30 weeks, 36 weeks

Population: Patients started dropping out at subsequent visits so the number analyzed at latter visits is less

See above in the primary outcome measure for a description of OACIS-I scale. This section describes the change from baseline of the OACIS-I subdomain of aberrant behaviors. This subdomain has a range of 1 to 7 - 1 is extremely improved from baseline, 7 is extremely worse from baseline, and 4 is no change. For analysis, the OACIS-I general score and subscale values were recoded, in which 4 (no change) was recoded as 0; 3 to 1 were recoded as +1 to +3 to denote improvement, and 5 to 7 were recoded as -1 to -3 for worsening.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
OACIS-I Response Rate on Aberrant Behaviors Subscale 7 weeks	0.06 score on a scale Standard Deviation 0.42	0.28 score on a scale Standard Deviation 0.57
OACIS-I Response Rate on Aberrant Behaviors Subscale 15 weeks	0.22 score on a scale Standard Deviation 0.43	0.33 score on a scale Standard Deviation 0.69
OACIS-I Response Rate on Aberrant Behaviors Subscale 22 weeks	0.59 score on a scale Standard Deviation 0.80	0.53 score on a scale Standard Deviation 0.87
OACIS-I Response Rate on Aberrant Behaviors Subscale 30 weeks	0.63 score on a scale Standard Deviation 0.89	0.59 score on a scale Standard Deviation 0.84
OACIS-I Response Rate on Aberrant Behaviors Subscale 36 weeks	0.14 score on a scale Standard Deviation 0.77	0.14 score on a scale Standard Deviation 0.53

SECONDARY outcome

Timeframe: 7 weeks, 15 weeks, 22 weeks, 30 weeks, 36 weeks

Population: Patients started dropping out at subsequent visits so the number analyzed at latter visits is less

See above in the primary outcome measure for a description of OACIS-I scale. This section describes the change from baseline of the OACIS-I subdomain of social communication. This subdomain has a range of 1 to 7 - 1 is extremely improved from baseline, 7 is extremely worse from baseline, and 4 is no change. For analysis, the OACIS-I general score and subscale values were recoded, in which 4 (no change) was recoded as 0; 3 to 1 were recoded as +1 to +3 to denote improvement, and 5 to 7 were recoded as -1 to -3 for worsening.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
OACIS-I Response Rate on Social Communication Subscale 7 weeks	0.33 score on a scale Standard Deviation 0.69	0.56 score on a scale Standard Deviation 0.70
OACIS-I Response Rate on Social Communication Subscale 15 weeks	0.44 score on a scale Standard Deviation 0.70	0.56 score on a scale Standard Deviation 0.62
OACIS-I Response Rate on Social Communication Subscale 22 weeks	0.65 score on a scale Standard Deviation 0.79	1.35 score on a scale Standard Deviation 0.61
OACIS-I Response Rate on Social Communication Subscale 30 weeks	0.94 score on a scale Standard Deviation 0.83	1.25 score on a scale Standard Deviation 0.61
OACIS-I Response Rate on Social Communication Subscale 36 weeks	0.32 score on a scale Standard Deviation 0.61	0.61 score on a scale Standard Deviation 0.66

SECONDARY outcome

Timeframe: 7 weeks, 15 weeks, 22 weeks, 30 weeks, 36 weeks

Population: Patients started dropping out at subsequent visits so the number analyzed at later visits is less

Aberrant Behavior Checklist (ABC) is a 58 item scale that primarily evaluates how aberrant or abnormal a patient's daily behaviors are. The items evaluate behaviors as they pertain to irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech. Each item is scored on a scale of 0 to 3, with 0 being better outcome and 3 being worse outcome. The score from each item is added up to calculate a total score. This outcome describes change in total ABC score from baseline at each follow up visit. The scores from all items are added to calculate a total score (0 to 174). This outcome describes change in total ABC score from baseline at each follow up visit.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
Change in Total Aberrant Behavior Checklist Score From Baseline 7 weeks	-6 score on a scale Standard Deviation 3.4	-16.23 score on a scale Standard Deviation 14.02
Change in Total Aberrant Behavior Checklist Score From Baseline 15 weeks	-22.6 score on a scale Standard Deviation 10.34	-11.68 score on a scale Standard Deviation 5.40
Change in Total Aberrant Behavior Checklist Score From Baseline 22 weeks	-36.33 score on a scale Standard Deviation 14.55	-22.4 score on a scale Standard Deviation 15.45
Change in Total Aberrant Behavior Checklist Score From Baseline 30 weeks	-22.8 score on a scale Standard Deviation 13.5	-10.29 score on a scale Standard Deviation 9.97
Change in Total Aberrant Behavior Checklist Score From Baseline 36 weeks	1.14 score on a scale Standard Deviation 3.53	-7.8 score on a scale Standard Deviation 5.56

SECONDARY outcome

Timeframe: 7 weeks, 15 weeks, 22 weeks, 30 weeks, 36 weeks

Population: Patients dropped out (or families did not return forms) at subsequent visits so the number analyzed at later visits is less.

The Social Responsiveness Scale-2 (SRS-2) is a 65-item scale that measures total scores as well as subscales: four social behaviors (awareness, cognition, communication and motivation) and autistic mannerisms. Each item is rated from 1 to 4 (not true to almost always true) on worksheets that are blinded to the rater with respect to values. Total and subscale scores are calculated as raw scores and can be converted to T-scores. Raw scores (range 0-180) are reported here (unadjusted for general population, since all children had ASD). Higher or lower values at follow up visits compared to baseline indicated worsening or improvement, respectively.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
Change in Total SRS-2 Score From Baseline 15 weeks	-16.86 score on a scale Standard Deviation 10.56	-7.92 score on a scale Standard Deviation 4.45
Change in Total SRS-2 Score From Baseline 22 weeks	-14.61 score on a scale Standard Deviation 9.90	-13.67 score on a scale Standard Deviation 11.23
Change in Total SRS-2 Score From Baseline 7 weeks	1.14 score on a scale Standard Deviation 5.33	-8.06 score on a scale Standard Deviation 7.89
Change in Total SRS-2 Score From Baseline 30 weeks	-19.83 score on a scale Standard Deviation 15.0	-18.59 score on a scale Standard Deviation 11.57
Change in Total SRS-2 Score From Baseline 36 weeks	0.80 score on a scale Standard Deviation 3.30	-19.59 score on a scale Standard Deviation 10.17

SECONDARY outcome

Timeframe: Week 0, Week 7, Week 15, Week 22, Week 30, Week 36

Population: Number analyzed varied due to participants who dropped out, their blood samples could not be obtained, or data could not be obtained from the assay.

Sulforaphane (and other isothiocyanates, ITC) are conjugated by glutathione (GSH) which then undergoes further enzymatic modifications to give rise sequentially to the cysteinylglycine-, cysteine- and N-acetylcysteine-ITC conjugates, all of which are dithiocarbamates (DTC) and are detected in the cyclocondensation reaction-HPLC assay.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=24 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
Dithiocarbamate Plasma Concentration Detected by Cyclocondensation at Each Visit Week 0	0.007 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.008	0.006 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.008
Dithiocarbamate Plasma Concentration Detected by Cyclocondensation at Each Visit Week 7	0.299 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.297	0.003 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.005
Dithiocarbamate Plasma Concentration Detected by Cyclocondensation at Each Visit Week 15	0.329 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.350	0.005 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.008
Dithiocarbamate Plasma Concentration Detected by Cyclocondensation at Each Visit Week 22	0.248 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0,232	0.205 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.253
Dithiocarbamate Plasma Concentration Detected by Cyclocondensation at Each Visit Week 30	0.165 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.183	0.214 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.228
Dithiocarbamate Plasma Concentration Detected by Cyclocondensation at Each Visit Week 36	0.015 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.024	0.008 nmol DTC (Dithiocarbamates)/ml Standard Deviation 0.012

SECONDARY outcome

Timeframe: Week 0 and Week 15

F-statistic calculated by comparison of Free Reduced GSH, Total GSH and oxidized Glutathione (GSSG) of Week 15 to Week 0.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
Comparison of Free Reduced Glutathione (GSH), Total GSH, Oxidized Glutathione (GSSG) at Week 0 and 15 Free Reduced GSH	1.51 F-statistic	0.11 F-statistic
Comparison of Free Reduced Glutathione (GSH), Total GSH, Oxidized Glutathione (GSSG) at Week 0 and 15 Total GSH	0.00 F-statistic	0.08 F-statistic
Comparison of Free Reduced Glutathione (GSH), Total GSH, Oxidized Glutathione (GSSG) at Week 0 and 15 GSSG	1.97 F-statistic	0.46 F-statistic

SECONDARY outcome

Timeframe: Week 15

Ratios of free GSH:GSSG and total GSH:GSSG were calculated by obtaining ratios of f-statistic scores from baseline to week 15 between free reduced GSH and GSSG and between total GSH and GSSG.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
Free GSH:GSSG and Total GSH:GSSG Ratios at Week 15 Free GSH:GSSG	12.72 F-statistic	0.87 F-statistic
Free GSH:GSSG and Total GSH:GSSG Ratios at Week 15 Total GSH:GSSG	5.16 F-statistic	0.03 F-statistic

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0, Week 15, Week 30

Population: N varies due to missing data, variable clinic visits or assay failure.

Cytoprotective enzyme regulated by nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of cellular redox homeostasis and an inhibitor of a key pro-inflammatory pathway, of which both functions are critical factors in the neuropathology of ASD. Total cellular RNA was isolated from peripheral blood mononuclear cells (PBMCs) and complementary DNAs (cDNA) were synthesized. Quantitative real-time PCR analysis was performed using the Applied Biosystems QuantStudio™ 3 Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). Relative mRNA expression was normalized to GAPDH. Gene expression was calculated using the comparative 2-ΔΔCT method.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
NQO1: NAD(P)H:Quinone Oxidoreductase-1 Week 0 (baseline)	2.23 log fold change Standard Deviation 0.18	2.25 log fold change Standard Deviation 0.22
NQO1: NAD(P)H:Quinone Oxidoreductase-1 Week 15	2.19 log fold change Standard Deviation 0.16	2.14 log fold change Standard Deviation 0.20
NQO1: NAD(P)H:Quinone Oxidoreductase-1 Week 30	2.15 log fold change Standard Deviation 0.15	2.13 log fold change Standard Deviation 0.11

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0, Week 15, Week 30

Population: N varies due to missing data, variable clinic visits or assay failure.

xCT (SLC7A11): Cystine/glutamate antiporter encoded by the SLC7A11 gene.Total cellular RNA was isolated from peripheral blood mononuclear cells (PBMCs) and complementary DNAs (cDNA) were synthesized. Quantitative real-time PCR analysis was performed using the Applied Biosystems QuantStudio™ 3 Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). Relative mRNA expression was normalized to GAPDH. Gene expression was calculated using the comparative 2-ΔΔCT method.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
xCT Week 0	0.24 log fold change Standard Deviation 0.94	0.40 log fold change Standard Deviation 0.71
xCT Week 15	0.25 log fold change Standard Deviation 0.65	0.30 log fold change Standard Deviation 0.95
xCT Week 30	0.24 log fold change Standard Deviation 1.02	0.27 log fold change Standard Deviation 1.00

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0, Week 15, Week 30

Population: N varies due to missing data, variable clinic visits or assay failure

HO-1 (heme oxygenase 1): an essential and Nrf2-dependent enzyme in heme catabolism. Total cellular RNA was isolated from peripheral blood mononuclear cells (PBMCs) and complementary DNAs (cDNA) were synthesized. Quantitative real-time PCR analysis was performed using the Applied Biosystems QuantStudio™ 3 Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). Relative mRNA expression was normalized to GAPDH. Gene expression was calculated using the comparative 2-ΔΔCT method.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
HO-1 (Heme Oxygenase 1) Week 0	0.10 log fold change Standard Deviation 1.21	0.27 log fold change Standard Deviation 0.98
HO-1 (Heme Oxygenase 1) Week 15	0.74 log fold change Standard Deviation 0.69	0.55 log fold change Standard Deviation 0.48
HO-1 (Heme Oxygenase 1) Week 30	0.74 log fold change Standard Deviation 0.56	0.30 log fold change Standard Deviation 1.40

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0, Week 15, Week 30

Population: N varies due to missing data, variable clinic visits or assay failure.

HSP70 (Heat shock protein 70) was examined because it is upregulated by SF in vitro. Total cellular RNA was isolated from peripheral blood mononuclear cells (PBMCs) and complementary DNAs (cDNA) were synthesized. Quantitative real-time PCR analysis was performed using the Applied Biosystems QuantStudio™ 3 Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). Relative mRNA expression was normalized to GAPDH. Gene expression was calculated using the comparative 2-ΔΔCT method.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
HSP70 Week 0	1.11 log fold change Standard Deviation 0.29	0.99 log fold change Standard Deviation 0.43
HSP70 Week 15	1.33 log fold change Standard Deviation 0.43	1.14 log fold change Standard Deviation 0.30
HSP70 Week 30	1.23 log fold change Standard Deviation 0.34	1.20 log fold change Standard Deviation 0.40

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0, Week 15, Week 30.

Population: N varies due to missing data, variable clinic visits or assay failure

HSP27 (Heat shock protein 27) was examined because it is upregulated by SF in vitro. Total cellular RNA was isolated from peripheral blood mononuclear cells (PBMCs) and complementary DNAs (cDNA) were synthesized. Quantitative real-time PCR analysis was performed using the Applied Biosystems QuantStudio™ 3 Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). Relative mRNA expression was normalized to GAPDH. Gene expression was calculated using the comparative 2-ΔΔCT method.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
HSP27 Week 0	0.21 log fold change Standard Deviation 0.46	-0.13 log fold change Standard Deviation 0.98
HSP27 Week 15	0.21 log fold change Standard Deviation 0.63	-0.83 log fold change Standard Deviation 1.21
HSP27 Week 30	-0.47 log fold change Standard Deviation 1.21	-0.58 log fold change Standard Deviation 1.46

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0, Week 15, Week 30

Population: N varies due to missing data, variable clinic visits or assay failure.

IL-6 (interleukin 6) cytokine gene expression, a nuclear factor-kappa B - regulated inflammatory biomarker. Total cellular RNA was isolated from peripheral blood mononuclear cells (PBMCs) and complementary DNAs (cDNA) were synthesized. Quantitative real-time PCR analysis was performed using the Applied Biosystems QuantStudio™ 3 Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). Relative mRNA expression was normalized to GAPDH. Gene expression was calculated using the comparative 2-ΔΔCT method.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
IL-6 Week 0	1.76 log fold change Standard Deviation 0.39	1.82 log fold change Standard Deviation 0.30
IL-6 Week 15	2.05 log fold change Standard Deviation 0.28	1.87 log fold change Standard Deviation 0.42
IL-6 Week 30	1.99 log fold change Standard Deviation 0.23	2.08 log fold change Standard Deviation 0.22

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0, Week 15, Week 30

Population: N varies due to missing data, variable clinic visits or assay failure.

IL-1β: Interleukin-1 beta cytokine gene expression, a nuclear factor-kappa B - regulated inflammatory biomarker. Total cellular RNA was isolated from peripheral blood mononuclear cells (PBMCs) and complementary DNAs (cDNA) were synthesized. Quantitative real-time PCR analysis was performed using the Applied Biosystems QuantStudio™ 3 Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). Relative mRNA expression was normalized to GAPDH. Gene expression was calculated using the comparative 2-ΔΔCT method.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
IL-1β Week 0	0.90 log fold change Standard Deviation 1.16	1.14 log fold change Standard Deviation 1.11
IL-1β Week 15	1.45 log fold change Standard Deviation 0.59	1.47 log fold change Standard Deviation 0.50
IL-1β Week 30	1.50 log fold change Standard Deviation 0.49	1.59 log fold change Standard Deviation 0.43

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0, Week 15, Week 30

Population: N varies due to missing data, variable clinic visits or assay failure.

Cox-2 (cyclooxygenase-2): a nuclear factor-kappa B - regulated inflammatory biomarker. Total cellular RNA was isolated from peripheral blood mononuclear cells (PBMCs) and complementary DNAs (cDNA) were synthesized. Quantitative real-time PCR analysis was performed using the Applied Biosystems QuantStudio™ 3 Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). Relative mRNA expression was normalized to GAPDH. Gene expression was calculated using the comparative 2-ΔΔCT method.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
Cox-2 Week 0	0.14 log fold change Standard Deviation 0.86	-0.20 log fold change Standard Deviation 1.06
Cox-2 Week 15	-0.07 log fold change Standard Deviation 1.59	0.16 log fold change Standard Deviation 0.66
Cox-2 Week 30	-0.46 log fold change Standard Deviation 1.57	-0.17 log fold change Standard Deviation 1.17

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0, Week 15, Week 30

Population: N varies due to missing data, variable clinic visits or assay failure

TNF-α (Tumor necrosis factor alpha), a cytokine as inflammatory biomarker. Total cellular RNA was isolated from peripheral blood mononuclear cells (PBMCs) and complementary DNAs (cDNA) were synthesized. Quantitative real-time PCR analysis was performed using the Applied Biosystems QuantStudio™ 3 Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). Relative mRNA expression was normalized to GAPDH. Gene expression was calculated using the comparative 2-ΔΔCT method.

Outcome measures

Measure	Sulforaphane n=22 Participants Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 Participants Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
TNF-α Week 15	0.98 log fold change Standard Deviation 1.03	1.08 log fold change Standard Deviation 0.49
TNF-α Week 0	0.70 log fold change Standard Deviation 1.00	0.91 log fold change Standard Deviation 0.37
TNF-α Week 30	1.17 log fold change Standard Deviation 0.79	1.10 log fold change Standard Deviation 0.73

Adverse Events

Sulforaphane

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sulforaphane n=32 participants at risk Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 participants at risk Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
Endocrine disorders Hashimoto thyroiditis	0.00% 0/32 • The pilot study took place over 2 weeks for each of 10 participants. The main study took place over 2 years, 6 months; 1/1/16 - 6/30/18 for 45 participants, each of whom was assessed from screening (time 0), 7, 15, 22 and up to 36 weeks for the final visit. Participants in the pilot study were followed for adverse events during regular clinical visits for at least 12 months after the study and none were reported. Adverse event reporting followed clinicaltrials.gov Definitions.	4.3% 1/23 • Number of events 1 • The pilot study took place over 2 weeks for each of 10 participants. The main study took place over 2 years, 6 months; 1/1/16 - 6/30/18 for 45 participants, each of whom was assessed from screening (time 0), 7, 15, 22 and up to 36 weeks for the final visit. Participants in the pilot study were followed for adverse events during regular clinical visits for at least 12 months after the study and none were reported. Adverse event reporting followed clinicaltrials.gov Definitions.

Other adverse events

Measure	Sulforaphane n=32 participants at risk Sulforaphane (SF) will be administered once a day orally in an approximate dose of 1 µmol/lb (2.2 kg µmol/kg) body weight. Each SF tablet will contain 125 mg broccoli seed powder (equivalent to \~ 15 µmol SF). The total dose per day will depend on participants' body weight: 30-50 lb: 3 tablets (45 µmol/day) 50-70 lb: 4 tablets (60 µmol/day) 70-90 lb: 6 tablets (90 µmol/day) 90-110 lb: 7 tablets (105 µmol/day) 110-130 lb: 8 tablets (120 µmol/day) For pilot study, all participants (n=10) will receive SF for 14 days. For main clinical trial, 25 participants will randomly receive SF for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo to sulforaphane arm will take place, and all participants will receive SF from 15-30 weeks. Sulforaphane: See under active arm description	Placebo n=23 participants at risk Placebo tablets identical in size and similar in appearance to the active tablets will be used. Number of placebo tablets will be equivalent to the active tablets depending on participants' body weight. For the main clinical trial, 25 participants will be randomly allocated to receive placebo for 15 weeks (phase 1). During phase 2, a single-arm crossover from placebo arm to sulforaphane arm will take place, and all participants will receive sulforaphane from 15-30 weeks. Placebo: See under placebo arm description
Nervous system disorders insomnia	6.2% 2/32 • The pilot study took place over 2 weeks for each of 10 participants. The main study took place over 2 years, 6 months; 1/1/16 - 6/30/18 for 45 participants, each of whom was assessed from screening (time 0), 7, 15, 22 and up to 36 weeks for the final visit. Participants in the pilot study were followed for adverse events during regular clinical visits for at least 12 months after the study and none were reported. Adverse event reporting followed clinicaltrials.gov Definitions.	0.00% 0/23 • The pilot study took place over 2 weeks for each of 10 participants. The main study took place over 2 years, 6 months; 1/1/16 - 6/30/18 for 45 participants, each of whom was assessed from screening (time 0), 7, 15, 22 and up to 36 weeks for the final visit. Participants in the pilot study were followed for adverse events during regular clinical visits for at least 12 months after the study and none were reported. Adverse event reporting followed clinicaltrials.gov Definitions.
Nervous system disorders irritability	6.2% 2/32 • The pilot study took place over 2 weeks for each of 10 participants. The main study took place over 2 years, 6 months; 1/1/16 - 6/30/18 for 45 participants, each of whom was assessed from screening (time 0), 7, 15, 22 and up to 36 weeks for the final visit. Participants in the pilot study were followed for adverse events during regular clinical visits for at least 12 months after the study and none were reported. Adverse event reporting followed clinicaltrials.gov Definitions.	0.00% 0/23 • The pilot study took place over 2 weeks for each of 10 participants. The main study took place over 2 years, 6 months; 1/1/16 - 6/30/18 for 45 participants, each of whom was assessed from screening (time 0), 7, 15, 22 and up to 36 weeks for the final visit. Participants in the pilot study were followed for adverse events during regular clinical visits for at least 12 months after the study and none were reported. Adverse event reporting followed clinicaltrials.gov Definitions.
General disorders taste/smell	6.2% 2/32 • The pilot study took place over 2 weeks for each of 10 participants. The main study took place over 2 years, 6 months; 1/1/16 - 6/30/18 for 45 participants, each of whom was assessed from screening (time 0), 7, 15, 22 and up to 36 weeks for the final visit. Participants in the pilot study were followed for adverse events during regular clinical visits for at least 12 months after the study and none were reported. Adverse event reporting followed clinicaltrials.gov Definitions.	0.00% 0/23 • The pilot study took place over 2 weeks for each of 10 participants. The main study took place over 2 years, 6 months; 1/1/16 - 6/30/18 for 45 participants, each of whom was assessed from screening (time 0), 7, 15, 22 and up to 36 weeks for the final visit. Participants in the pilot study were followed for adverse events during regular clinical visits for at least 12 months after the study and none were reported. Adverse event reporting followed clinicaltrials.gov Definitions.
Gastrointestinal disorders gastrointestinal upset	6.2% 2/32 • The pilot study took place over 2 weeks for each of 10 participants. The main study took place over 2 years, 6 months; 1/1/16 - 6/30/18 for 45 participants, each of whom was assessed from screening (time 0), 7, 15, 22 and up to 36 weeks for the final visit. Participants in the pilot study were followed for adverse events during regular clinical visits for at least 12 months after the study and none were reported. Adverse event reporting followed clinicaltrials.gov Definitions.	0.00% 0/23 • The pilot study took place over 2 weeks for each of 10 participants. The main study took place over 2 years, 6 months; 1/1/16 - 6/30/18 for 45 participants, each of whom was assessed from screening (time 0), 7, 15, 22 and up to 36 weeks for the final visit. Participants in the pilot study were followed for adverse events during regular clinical visits for at least 12 months after the study and none were reported. Adverse event reporting followed clinicaltrials.gov Definitions.

Additional Information

Andrew Zimmerman, MD

Univ of Massachusetts Medical School

Phone: 4109350488

Email: andrew.zimmerman@umassmemorial.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place