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Pancreatic Replacement Therapy for Maladaptive Behaviors in Preschool Children With Autism Spectrum Disorder
Deborah A Pearson1, Robert L Hendren2, Matthew F Heil3
1Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, Houston, Texas.
Insights
High-protease pancreatic replacement therapy reduced irritability in preschool children with autism spectrum disorder (ASD). This study demonstrates a potential new treatment for core and associated symptoms of ASD.
Area of Science:
- Pediatric Gastroenterology
- Neurodevelopmental Disorders
- Clinical Trial Design
Background:
- Autism spectrum disorder (ASD) presents an urgent need for treatments targeting core and associated maladaptive symptoms, particularly in preschool-aged children.
- Existing treatments often focus on managing symptoms rather than addressing underlying mechanisms or core behavioral challenges.
Purpose of the Study:
- To evaluate the efficacy of high-protease pancreatic replacement therapy in improving autism-associated maladaptive behaviors in children aged 3 to 6 years.
- To assess both short-term and long-term effects of this therapeutic intervention on behavioral outcomes in young children with ASD.
Main Methods:
- A 32-site, US-based, double-blind, parallel-group, delayed-start cohort study.
- Participants received either high-protease pancreatic replacement therapy (900 mg) or placebo orally three times daily for 12 weeks, followed by an open-label phase.
- The Aberrant Behavior Checklist (ABC-I) for irritability/agitation was the primary outcome measure, assessed at 12 and 36 weeks.
Main Results:
- Statistically significant reductions in irritability were observed at both 12 weeks (-2.49, P=.03) and 36 weeks (-3.07, P=.03) compared to placebo.
- The treatment, high-protease pancreatic replacement (CM-AT), was well-tolerated, with no emergent safety concerns or serious adverse events reported.
- A moderate effect size (Cohen d=0.364 at 12 weeks, 0.516 at 36 weeks) indicated a meaningful clinical impact on irritability.
Conclusions:
- High-protease pancreatic replacement therapy demonstrated sustained cumulative reduction in irritability, a key maladaptive behavior in preschool children with ASD.
- The delayed-start analysis design proved effective in evaluating disease and condition modification, offering a valuable tool for future ASD treatment research.
- This intervention shows promise as a well-tolerated and effective option for managing behavioral symptoms in young children with autism spectrum disorder.
Importance:
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.
Objectives:
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.
Design, Setting, And Participants:
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.
Interventions:
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.
Main Outcomes And Measures:
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).
Results:
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.
Conclusions And Relevance:
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.
Trial Registration:
ClinicalTrials.gov Identifier: NCT02410902 and NCT02649959.
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