Clinical trial NCT05025553: Oral Administration of Polyethylene Glycol (PEG) for 6 Months in Chronically Constipated Autistic Children
Official title: Gut Mobilization With Oral Administration of Polyethylene Glycol (PEG) at the Dose of 6.9 g/d Once a Day for 6 Months in Chronically Constipated Autistic Children.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autistic Spectrum Disorder
Constipation
Keywords: Autism
4-cresol
anxiety
autism spectrum disorder
biomarkers
constipation
microbiota
Lead sponsor: University of Messina
Sponsor class: OTHER
First posted: 2021-08-27
Enrollment: 21
Sex: ALL
Minimum age (years): 2
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: In this open trial, each child underwent gut mobilization using a standard protocol with oral administration of PEG (6.9 g/d once a day) for 6 months. Children were observed and behaviorally tested at baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization.

At the time of recruitment, Intellectual Quotient (IQ) or Developmental Quotient (DQ) were determined using the Leiter International Performance Scale-Third Edition or the Griffith Mental Development Scales, respectively. Autistic behaviors were assessed using the ADOS-2, and the Children Autism Rating Scales (CARS). Adaptive functioning was assessed using the Vineland Adaptive Behavior Scales-Second Edition
Primary purpose: TREATMENT

Brief summary: Many autistic children suffer from chronic constipation. Gut mobilization was obtained administering polyethylene glycol (PEG) at the dose of 6.9 g/d once a day for 6 months in an open trial involving 21 chronically constipated autistic children 2-8 years old, followed prospectively for 6 months. Children diagnosed with Autism Spectrum Disorder by DSM-5 and confirmed by ADOS-2 criteria, were evaluated before (T0), 1 month (T1), and 6 months (T2) after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors, anxiety, and hyperactivity.

Detailed description: Chronic constipation is common among children with ASD and is associated with more severe anxiety, hyperactivity, irritability and repetitive behaviors. Young autistic children with chronic constipation display higher urinary and foecal concentrations of p-cresol, an aromatic compound produced by gut bacteria, known to negatively affect brain function. Acute p-cresol administration to BTBR mice enhances anxiety, hyperactivity and stereotypic behaviors, while blunting social interaction. This study was undertaken to prospectively assess the behavioral effects of gut mobilization in young autistic children with chronic constipation, and to verify their correlation with urinary p-cresol. To this aim, 21 chronically constipated autistic children 2-8 years old were evaluated before (T0), 1 month (T1), and 6 months (T2) after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors, anxiety, and hyperactivity. Gut mobilization was obtained administering PEG (6.9 g/d once a day) for 6 months. A progressive, statistically significant decrease in all behavioral symptoms was recorded over the six-month study period. Urinary p-cresol levels displayed variable trends, mainly increasing at T1 and decreasing at T2. These results support gut mobilization as a simple strategy to at least partly ameliorate ASD symptoms, as well as comorbid anxiety and hyperactivity, in chronically constipated children. These beneficial effects likely involve multiple mechanisms.

Eligibility criteria: Inclusion Criteria:

* Fulfilling DSM-5 diagnostic criteria for Autism Spectrum Disorder
* Chronic constipation, namely unsatisfactory defecation characterized by difficult and infrequent passage of lumpy and hard stools during at least the previous 3 months, as reported by parents based on the Bristol Stool Scale

Exclusion Criteria:

* ASD constipated children already treated with laxatives

Primary outcomes:
measure: Change in stool quality
timeFrame: At baseline (T0) prior to gut mobilization; 1 month (T1) and 6 months (T2) after gut mobilization
measure: Change from baseline urinary concentrations of total p-cresol
timeFrame: First-morning urines were collected at home by parents at baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization
measure: Change in Childhood Autism Rating Scale (CARS)
timeFrame: At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization
measure: Change in Repetitive Behavior Scale-Revised (RBS-R)
timeFrame: At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization
measure: Change in Conners' Parent Rating Scale - Revised (CPRS-R)
timeFrame: At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization
measure: Change in Social Responsiveness Scale (SRS)
timeFrame: At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization
Secondary outcomes:
Other outcomes:
Locations:
city: Messina
country: Italy
facility: Interdipartimental Program "Autismo 0-90" at "G. Martino" University Hospital
state: ME
Study officials:
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