Pancreatic Replacement Therapy with CM-at Is Associated with Reduction in Maladaptive Behaviors in Preschoolers with Autism.

Poster Presentation
Friday, May 3, 2019: 5:30 PM-7:00 PM
Room: 710 (Palais des congres de Montreal)
M. F. Heil1, D. A. Pearson2, R. Hendren3, S. R. Raines4 and J. Fallon1, (1)Curemark, LLC, Rye, NY, (2)McGovern Medical School, Univ. TX Health Sci Cntr-Houston, Houston, TX, (3)Psychiatry, University of California, San Francisco, San Francisco, CA, (4)2b Analytics, LLC, Wallingford, PA

Many children with autism exhibit self-restrictive dietary patterns, particularly avoidance of protein. Previous studies by our group suggest that this behavior may reflect digestive impairment associated with abnormally low levels of the enzyme chymotrypsin in some children with autism (e.g., Heil et al, 2014). Chymotrysin is needed to digest protein, and a lower endogenous level of it results in a reduced ability to break down protein into its component amino acids. As a result of this deficiency, there might be lower levels of amino acids available to synthesize new proteins such as neurotransmitters--which in turn might ultimately affect behavioral status. This deficiency would be particularly problematic in rapidly growing preschoolers. If this digestive insufficiency could be normalized with dietary enzymatic replacement therapy, it may result in improved behavioral function in children with autism.


The objective of this study was to ascertain whether or not behavior (e.g., symptoms of irritability, hyperactivity) in preschoolers with autism could be improved with CM-AT, a pancreatic enzyme preparation.


Preschoolers (n=190) ages 3-5 years old, meeting DSM-IV-TR criteria for Autistic Disorder, participated in this randomized, placebo-controlled, 12-week clinical trial of CM-AT. Children entering the trial were required to have a score of ≥11 on the Aberrant Behavior Checklist-Irritability scale (ABC-I). Following a 2-week placebo run-in, children were randomized to either CM-AT (n=92, 71 boys), which was delivered as granules sprinkled on food, or to placebo (n=98, 79 boys), which consisted of visually identical inert sprinkles. The primary outcome measure for this trial was ABC-Irritability (ABC-I). Here we report all the ABC data in this 12-week trial.


Mixed model repeated measures (MMRM) procedures revealed that children receiving CM-AT (relative to those receiving placebo) demonstrated significant reductions in Irritability (ABC-I: p=.038); Hyperactivity (ABC-HA: p=.049; Inappropriate Speech (ABC-IS: p=.015) over the 12 weeks of the trial. Additional MMRM analyses were performed examining treatment response in a subset of preschoolers (n=69) with higher levels of irritability (ABC-I ≥18+) and greater overall clinical severity (CGI-S≥4) at baseline. In this more severely affected subgroup, the 29 preschoolers who received CM-AT (relative to the 40 who received placebo), the significance of the treatment effects for Irritability and Hyperactivity were even greater than those found in the overall sample (ABC-I: p= .022; ABC-HA: p=.027). Although reductions in Lethargy/Social Withdrawal (ABC-L/SW) and Stereotypic Behavior (ABC-S) were also noted during the course of this 12-week trial for both the overall sample and for the more severe subsample, no statistically significant treatment effects emerged for these symptoms in this 12-week treatment trial.


These results suggest that even within the short timeframe of 12 weeks, children with autism who received pancreatic enzymatic replacement therapy with CM-AT demonstrated reductions in maladaptive behaviors commonly associated with autism (e.g., irritability, hyperactivity, inappropriate speech). These effects were even more pronounced in a subset of preschoolers with autism who had higher levels of initial irritability and global clinical ratings of maladaptive behavior. Long-term effects of CM-AT are continuing to be studied in an open label follow-up study.