Pancreatic Replacement Therapy for Maladaptive Behaviors in Preschool Children With Autism Spectrum Disorder.
Pancreatic enzyme capsules give modest, lasting cuts in irritability for preschoolers with ASD.
01Research in Context
What this study did
The team ran a placebo-controlled trial with preschoolers who have autism.
Kids got either high-protease pancreatic enzymes or a dummy pill three times a day.
Parents and clinicians tracked irritability scores for 36 weeks.
What they found
By week 12 the enzyme group showed a small but real drop on the irritability scale.
The gain stayed through week 36 and no serious side effects were reported.
How this fits with other research
Crossman et al. (2018) tested riluzole for the same irritability target and saw no change.
The two pills clashed on outcome, but K’s kids were older and the trial was shorter.
Taylor et al. (2017) got large behavior drops using PBS plus CBT in children who also had ID.
That looks like a contradiction, yet their kids had more severe issues and got active coaching, not pills.
Dababnah et al. (2025) added parent tele-training and saw small child gains similar to the enzyme effect, hinting you can stack parent work on top of enzymes.
Why it matters
You now have a second biological option that can trim irritability in preschool clients.
Pair the enzyme with parent coaching or PBS plans to chase bigger, faster change.
Always rule out GI pain first, then track irritability weekly to see if the pill is worth the cost.
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02At a glance
03Original abstract
<h4>Importance</h4>There is an urgent unmet need for a treatment addressing the core symptoms and associated maladaptive symptoms of autism spectrum disorder (ASD), especially in preschool populations.<h4>Objectives</h4>To evaluate whether treatment of children with ASD aged 3 to 6 years treated with high-protease pancreatic therapy produces long- and short-term improvements in autism-associated maladaptive behaviors.<h4>Design, setting, and participants</h4>This cohort study at 32 sites across the US used a double-blind parallel group, delayed-start design comprising a 2-week blinded placebo run-in, and a double-blind, randomized, placebo-controlled segment (12 weeks). Children were recruited into the study in 2015, with data collection continuing until 2021. The analyses were completed from June 2021 to February 2022.<h4>Interventions</h4>All participants were randomly assigned to receive either 900 mg high-protease pancreatic replacement therapy or placebo with food 3 times a day for 12 weeks, followed by all receiving 900 mg high-protease pancreatic replacement therapy for 24 weeks.<h4>Main outcomes and measures</h4>The primary outcome was the irritability/agitation subscale of the Aberrant Behavior Checklist (ABC-I). All potential participants were screened using the Social Communication Questionnaire (SCQ) with diagnosis confirmed by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) for ASD and the Autism Diagnostic Inventory-Revised (ADI-R). Outcomes were measured at the conclusion of the 12-week double-blind segment and at the conclusion of the 24-week open-label segment (total 36 weeks).<h4>Results</h4>A total of 190 participants (150 male [79%]), aged 3 to 6 (mean [SD] age, 4.5 [0.8]) years were randomized. Mixed model for repeated measures analysis performed on ABC-I demonstrated statistically significant differences of -2.49 (95% CI, -4.66 to -0.32; Cohen d = 0.364; P = .03) at the 12-week timepoint and -3.07 (95% CI, -5.81 to -0.33; Cohen d = 0.516; P = .03) at 36-week timepoint. No convergence was noted. Our high-protease pancreatic replacement (CM-AT) was well tolerated with no emergent safety concerns or related serious adverse events noted.<h4>Conclusions and relevance</h4>This cohort study of preschool children sustained cumulative reduction in the maladaptive behavior of irritability in autism. This delayed-start analysis, used to demonstrate disease and condition modification, may prove to be an important tool to evaluate treatments for ASD.<h4>Trial registration</h4>ClinicalTrials.gov Identifier: NCT02410902 and NCT02649959.
, 2023 · doi:10.1001/jamanetworkopen.2023.44136