Phase 2
N=10
Sulforaphane Treatment of Children With Autism Spectrum Disorder (ASD)
Autism Spectrum Disorder
Bottom Line
View on ClinicalTrials.gov: NCT02561481 ↗Enrolled (actual)
10
Serious AEs
1.8%
Results posted
Nov 2020
Primary outcome: Primary: Change in Ohio Autism Clinical Impressions Scale - Improvement (OACIS-I) Average Score From Baseline — 0.28; 0.28; 0.28; 0.33 score on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Sulforaphane (Drug); Placebo (Drug)
- Age
- Pediatric · 3+ yrs
- Sex
- All
- Sponsor
- University of Massachusetts, Worcester
- Primary completion
- Dec 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Ohio Autism Clinical Impressions Scale - Improvement (OACIS-I) Average Score From Baseline |
0.28; 0.28; 0.28; 0.33; 0.47; 0.59 | — |
| SECONDARY OACIS-I Response Rate on Aberrant Behaviors Subscale |
0.06; 0.28; 0.22; 0.33; 0.59; 0.53 | — |
| SECONDARY OACIS-I Response Rate on Social Communication Subscale |
0.33; 0.56; 0.44; 0.56; 0.65; 1.35 | — |
| SECONDARY Change in Total Aberrant Behavior Checklist Score From Baseline |
-6; -16.23; -22.6; -11.68; -36.33; -22.4 | — |
| SECONDARY Change in Total SRS-2 Score From Baseline |
1.14; -8.06; -16.86; -7.92; -14.61; -13.67 | — |
| SECONDARY Dithiocarbamate Plasma Concentration Detected by Cyclocondensation at Each Visit |
0.007; 0.006; 0.299; 0.003; 0.329; 0.005 | — |
| SECONDARY Comparison of Free Reduced Glutathione (GSH), Total GSH, Oxidized Glutathione (GSSG) at Week 0 and 15 |
1.51; 0.11; 0.00; 0.08; 1.97; 0.46 | — |
| SECONDARY Free GSH:GSSG and Total GSH:GSSG Ratios at Week 15 |
12.72; 0.87; 5.16; 0.03 | — |
Summary
ASD is a diverse disorder starting in early childhood and characterized by social communication impairment as well as restricted interests and repetitive behaviors. It affects 1:68 children and is an enormous medical and economic problem for which there is no established, mechanism-based treatment. Sulforaphane is an isothiocyanate derived from broccoli, and has potent activity in transcriptionally up-regulating genes that control mechanisms whereby aerobic cells protect themselves against oxidative stress, mitochondrial dysfunction, and inflammation.
This study is a clinical trial of oral sulforaphane (as broccoli seed powder) in 50 boys and girls (3-12 years) with ASD in 3 phases over 36 weeks. In Phase 1, 25 children will receive active drug and 25 will receive placebo for 15 weeks; in Phase 2, all children will receive sulforaphane from 15-30 weeks; in Phase 3, children will receive no treatment for 6 weeks. Study visits will take place at screening, 7, 15, 22, 30 and 36 weeks, when the Ohio Autism Clinical Clinical Impressions Scale - Severity and Improvement (OACIS-S and OACIS-I), Aberrant Behavior Checklist (ABC) and Social Responsiveness Scale (SRS) will be recorded. Children will be monitored with physical examinations and for toxicity with clinical laboratory studies and examine possible biomarkers: Nuclear factor-erythroid factor 2 (Nrf2), oxidative stress and mitochondrial function, the mechanistic target of rapamycin (mTOR) pathway and cytokine expression. In addition, prior to the main clinical trial, a pilot study will be carried out in 10 children with ASD, 6-12 years of age, who will receive sulforaphane, 2.2 micromoles/kg daily for 14 days. Blood and urine samples before and at the end of treatment will be collected, in order to measure several parameters that are likely to demonstrate expected effects of sulforaphane, to standardize the assays and procedures, and to determine the most effective measures.
Eligibility Criteria
Inclusion Criteria
- Autism Spectrum Disorder (ASD) diagnosis of moderate or greater severity
- Age 3 through 12 years inclusive
Exclusion Criteria
- Absence of a parent or legal guardian and consent
- Inability to speak/understand English language
- Seizure within 1 year of screening: This exclusion is based on the theoretical concern that cellular activation by sulforaphane might exacerbate seizures in patients with known seizure disorders. As noted in our previous trial of sulforaphane in young adult males, a seizure occurred in each of 2 participants: one during treatment (in a participant with a previously undisclosed seizure), the other 3 weeks after discontinuing sulforaphane.
- Impaired renal function (serum creatinine > 1.2 mg/dl), impaired hepatic function (SGOT/SGPT> 2x upper limit of normal), impaired thyroid function (Thyroid Stimulating Hormone (TSH) outside normal limits): This exclusion is based on a theoretical possibility of activation of underlying cellular metabolic abnormalities by sulforaphane. Current infection or treatment with antibiotics: this exclusion is to avoid complications of inter-current illness that may occur due to the clinical trial or obscure possible effects of sulforaphane.
- Medications that may modify the course or testing of ASD parameters (e.g., prednisone): This exclusion is necessary in order not to interfere with or complicate effects of sulforaphane.
- Chronic medical disorder (e.g., cardiovascular disease, stroke or diabetes) or major surgery within 3 months prior to enrollment: Serious medical illness in the child may be complicated by the clinical trial and make it difficult to discern a change in ASD associated with treatment.
- Less than 3 years or more than 13 years of age: this age range was selected to cover the ages from usual diagnosis of ASD up to adolescence.
- A diagnosis of autism spectrum disorder of mild severity (for example, earlier categories of Asperger disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS)), according to Autism Diagnostic Observation Schedule (ADOS) criteria.
- Prisoners
- Pregnant women
Data sourced from ClinicalTrials.gov (NCT02561481). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.