Effects of Intravenous Secretin on Language and Behavior of Children With Autism and Gastrointestinal Symptoms: A Single-Blinded, Open-Label Pilot Study

Abstract

ABSTRACT. Background. Autism is a severe developmental disorder with poorly understood etiology. A recently published case series describes 3 autistic children with gastrointestinal symptoms who underwent endoscopy and intravenous administration of secretin and were subsequently noted by their parents to demonstrate improved language skills over a 5-week period. This report sparked tremendous public interest, and investigators at several sites moved quickly to design controlled trials to test the efficacy of secretin as a therapy for autistic children. However, this is the first effort specifically designed to replicate the initial reported findings in terms of patient age, presenting symptoms, and drug administration.Objective. To rigorously apply the scientific method by assessing the reproducibility of the reported effects of intravenous secretin on the language of young children with autism and gastrointestinal symptoms.Methods. We performed a single-blinded, prospective, open-label trial by conducting formal language testing and blinded behavioral rating both before and repeatedly after a standardized infusion of secretin. We selected autistic children who were similar in age and profile to those described in the published retrospective case review. Inclusion criteria for study participation included age (3-6 years), confirmed diagnosis of autism, and reported gastrointestinal symptoms (16 had chronic diarrhea, 2 had gastroesophageal reflux, and 2 had chronic constipation). Twenty children (18 male) were admitted to the Pediatric Clinical Research Center at the University of California, San Francisco after administration of the Preschool Language Scale-3 (PLS-3). A 3 CU/kg dose of secretin (Secretin-Ferring) was administered intravenously (upper endoscopy was not performed). Behavioral ratings were derived using the Autism Observation Scale applied to a 30-minute time sample of the child's behavior consisting of a videotape of the PLS-3 (structured setting) and a second free play session with a standard set of developmentally appropriate toys. Participants then returned for follow-up evaluations, with readministrations of the PLS-3 at 1, 2, 3, and 5 weeks' postinfusion, and videotaping of each session for later blinded review by 2 independent observers using the Autism Observation Scale, uninformed about week of posttreatment. We also surveyed parents of our study children about their impressions of the effects of secretin using a 5-point Likert scale for parents to rate changes seen in their child.Results. With a total study completion rate across all participants of 96%, repeated measures analyses of variance revealed no significant increases in children's language skills from baseline across all 5 study time periods after a single infusion of secretin. Similarly, neither significant decreases in atypical behaviors nor increases in prosocial behaviors and developmentally appropriate play skills emerged. Furthermore, no relationship was found between parental reports of change and observable improvement in...

The role of a language scale for infant and preschool assessment

“…Results verified the test-retest stability of PLS (raw scores reported) but failed to support the value of the medication [Dunn-Geier et al, 2000;Lightdale et al, 2001]. Children with hearing loss related to a medical diagnosis such as otitis media have been assessed to see how language learning has been affected [Petinou et al, 2001].…”

Class II G Protein-Coupled Receptors and Their Ligands in Neuronal Function and Protection

“…Subsequent controlled studies in autism (Dunn-Geier et al, 2000;Lightdale et al, 2001;Owley et al, 2001), have either failed to confirm the Horvath study, or have demonstrated a modest trend toward behavioral improvements (Coniglio et al, 2001). Secretin has also been described as being potentially therapeutic for disorders distantly related to autism such as schizophrenia (Sheitman et al, 2004).…”

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“…Many studies (e.g., Carey et al, 2002;Coniglio et al, 2001;Lightdale et al, 2001;Molloy et al, 2002;Roberts et al, 2001;Unis et al, 2002) have cited GI problems in their participants and several (Lightdale et al; Roberts et al; Unis et al) attempted to identify a possible subtype for whom secretin might prove effective. However, none found significant differences that could provide clinical indicators.…”

“…The Kern et al (2002) findings are noteworthy because they suggest there may be a subgroup of children with autism whose symptoms could be diminished by secretin. Nevertheless, they are in contrast to the study by Carey et al who used the same outcome measure (the ABC) and reported worse scores on two of the same subtests (hyperactivity and inappropriate speech) that were reported by Kern et al to have improved. A pilot study by Lightdale et al (2001) attempted to replicate the Horvath et al (1998) findings and address the issue of a possible subgroup of responders with specific GI complaints. Porcine secretion was infused in an uncontrolled, open-label trial with participants who were followed for 5 weeks.…”