Zimmerman · 2021 · Molecular autism
Primary and secondary outcomes in a 15-week pediatric trial
Did the clinician-rated primary and caregiver-rated secondary outcomes reach the same conclusion?
Human · randomized double-blind controlled trial
Key findings
Results of the 15-week placebo comparison
The primary OACIS ratings of overall autism at weeks seven and 15 were not significant. A between-group difference appeared in secondary ABC at week 15, but SRS-2 was not significant.
Primary and Secondary Outcomes
Initial randomized controlled phase · 15 weeks
- Primary outcome OACIS
- Not significant
- Secondary outcome ABC
- Significant
- Secondary outcome SRS-2
- Not significant
Primary outcome: OACIS · secondary outcomes: ABC and SRS-2
Results of the initial 15-week placebo comparison.
Read the original paper and sources ↓Detailed results
Only the first 15 weeks of the 36-week study directly compared treatment with placebo.
Fifty-seven children aged 3–12 years were randomized; most analyses used the 45 who completed 15 weeks (22 SFN, 23 placebo). Both groups received sulforaphane material during weeks 16–30, followed by six weeks without intake.
The primary assessment was clinician-rated OACIS-I, and secondary assessments were caregiver-rated ABC and SRS-2. Even for the same child, overall clinical ratings, problem behavior, and social responsiveness measure different aspects.
| Assessment | Difference between sulforaphane and placebo | Meaning |
|---|---|---|
| OACIS-I overall assessment · primary | d=0.10, 95% CI −0.52~0.72 | No significant difference |
| ABC total score · secondary | d=−0.96, 95% CI −1.73~−0.15 | Greater reduction in the sulforaphane group |
| SRS-2 · secondary | No significant between-group difference | Improvement in social responsiveness not established |
Cohen's d expresses score differences as an effect size in standard-deviation units. The scales differ in what they measure and the direction of scores.
Cellular energy and inflammatory responses were examined alongside behavior changes.
Differences at week 15 were also reported for the ABC hyperactivity/inattention and inappropriate speech subscales. In a separate analysis of 27 participants with valid blood-cell data, mitochondrial respiration related to ATP production increased in the sulforaphane group. Changes in some inflammation-related genes were also observed.
Behavioral ratings and biological responses in blood cells were observed together to explore associations between them.
Outcomes and study formulation
There were early withdrawals and missing data at different time points, and multiple measures were explored. Secondary ABC improved, while primary OACIS was not significant. The later phase was open-label, with participants aware of intake.
The tablets provided both glucoraphanin and active myrosinase. A 2021 correction revised the ingredient description to state an expected yield of at least approximately 15 µmol sulforaphane from 34 µmol glucoraphanin per tablet.
Study design
Tablets were compared with placebo for the initial 15 weeks, after which both groups entered an open-label intake phase. Intake then stopped for six weeks while behavior and blood and urine biomarkers were observed.
- Participants
- Fifty-seven children with ASD randomized · ages 3–12
45 analyzed: 22 SFN / 23 placebo - Intake and observation
- Tablets containing GLR and active myrosinase
15-week controlled trial + 15-week open-label intake + six-week discontinuation - Measures
- Primary OACIS clinician assessment, secondary caregiver-rated ABC and SRS-2, and biomarkers
Study context
Forty-five participants were analyzed, excluding missing data. The primary clinical assessment was OACIS, with caregiver-rated ABC and SRS-2 as secondary measures.
Original paper and sources
Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder.
- Journal
- Molecular autism · 2021 · 12(1): 38
- First published
- 2021-05-25
2021 correction notice · The ingredient description was corrected to specify 34 µmol GLR and active myrosinase per tablet, with an expected yield of at least approximately 15 µmol SFN.