Oral Administration of Polyethylene Glycol (PEG) for 6 Months in Chronically Constipated Autistic Children

NCT ID: NCT05025553

Last Updated: 2021-08-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-01

Study Completion Date

2021-02-01

Brief Summary

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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

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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.

Conditions

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Autistic Spectrum Disorder Constipation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Gut mobilization

Polyethylene Glycol (PEG) at the dose of 6.9 g/d once a day for 6 months.

Group Type OTHER

Gut mobilization

Intervention Type DIETARY_SUPPLEMENT

Polyethylene Glycol (PEG) at the Dose of 6.9 g/d Once a Day for 6 Month. Children were observed and tested at baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization.

Interventions

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Gut mobilization

Polyethylene Glycol (PEG) at the Dose of 6.9 g/d Once a Day for 6 Month. Children were observed and tested at baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Maximum Eligible Age

8 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Messina

OTHER

Sponsor Role lead

Responsible Party

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Antonio Persico

Full Professor in Child & Adolescent Neuropsychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Interdipartimental Program "Autismo 0-90" at "G. Martino" University Hospital

Messina, ME, Italy

Site Status

Countries

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Italy

References

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Gorrindo P, Williams KC, Lee EB, Walker LS, McGrew SG, Levitt P. Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res. 2012 Apr;5(2):101-8. doi: 10.1002/aur.237.

Reference Type BACKGROUND
PMID: 22511450 (View on PubMed)

Goodhart PJ, DeWolf WE Jr, Kruse LI. Mechanism-based inactivation of dopamine beta-hydroxylase by p-cresol and related alkylphenols. Biochemistry. 1987 May 5;26(9):2576-83. doi: 10.1021/bi00383a025.

Reference Type BACKGROUND
PMID: 3607034 (View on PubMed)

Kang DW, Adams JB, Vargason T, Santiago M, Hahn J, Krajmalnik-Brown R. Distinct Fecal and Plasma Metabolites in Children with Autism Spectrum Disorders and Their Modulation after Microbiota Transfer Therapy. mSphere. 2020 Oct 21;5(5):e00314-20. doi: 10.1128/mSphere.00314-20.

Reference Type BACKGROUND
PMID: 33087514 (View on PubMed)

Kashyap PC, Marcobal A, Ursell LK, Larauche M, Duboc H, Earle KA, Sonnenburg ED, Ferreyra JA, Higginbottom SK, Million M, Tache Y, Pasricha PJ, Knight R, Farrugia G, Sonnenburg JL. Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice. Gastroenterology. 2013 May;144(5):967-77. doi: 10.1053/j.gastro.2013.01.047. Epub 2013 Feb 1.

Reference Type BACKGROUND
PMID: 23380084 (View on PubMed)

Altieri L, Neri C, Sacco R, Curatolo P, Benvenuto A, Muratori F, Santocchi E, Bravaccio C, Lenti C, Saccani M, Rigardetto R, Gandione M, Urbani A, Persico AM. Urinary p-cresol is elevated in small children with severe autism spectrum disorder. Biomarkers. 2011 May;16(3):252-60. doi: 10.3109/1354750X.2010.548010. Epub 2011 Feb 18.

Reference Type BACKGROUND
PMID: 21329489 (View on PubMed)

De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, Cristofori F, Guerzoni ME, Gobbetti M, Francavilla R. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One. 2013 Oct 9;8(10):e76993. doi: 10.1371/journal.pone.0076993. eCollection 2013.

Reference Type BACKGROUND
PMID: 24130822 (View on PubMed)

Gabriele S, Sacco R, Altieri L, Neri C, Urbani A, Bravaccio C, Riccio MP, Iovene MR, Bombace F, De Magistris L, Persico AM. Slow intestinal transit contributes to elevate urinary p-cresol level in Italian autistic children. Autism Res. 2016 Jul;9(7):752-9. doi: 10.1002/aur.1571. Epub 2015 Oct 6.

Reference Type BACKGROUND
PMID: 26437875 (View on PubMed)

Gabriele S, Sacco R, Cerullo S, Neri C, Urbani A, Tripi G, Malvy J, Barthelemy C, Bonnet-Brihault F, Persico AM. Urinary p-cresol is elevated in young French children with autism spectrum disorder: a replication study. Biomarkers. 2014 Sep;19(6):463-70. doi: 10.3109/1354750X.2014.936911. Epub 2014 Jul 10.

Reference Type BACKGROUND
PMID: 25010144 (View on PubMed)

Pascucci T, Colamartino M, Fiori E, Sacco R, Coviello A, Ventura R, Puglisi-Allegra S, Turriziani L, Persico AM. P-cresol Alters Brain Dopamine Metabolism and Exacerbates Autism-Like Behaviors in the BTBR Mouse. Brain Sci. 2020 Apr 13;10(4):233. doi: 10.3390/brainsci10040233.

Reference Type BACKGROUND
PMID: 32294927 (View on PubMed)

Persico AM, Ricciardello A, Lamberti M, Turriziani L, Cucinotta F, Brogna C, Vitiello B, Arango C. The pediatric psychopharmacology of autism spectrum disorder: A systematic review - Part I: The past and the present. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Aug 30;110:110326. doi: 10.1016/j.pnpbp.2021.110326. Epub 2021 Apr 20.

Reference Type BACKGROUND
PMID: 33857522 (View on PubMed)

Gevi F, Zolla L, Gabriele S, Persico AM. Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism. Mol Autism. 2016 Nov 24;7:47. doi: 10.1186/s13229-016-0109-5. eCollection 2016.

Reference Type RESULT
PMID: 27904735 (View on PubMed)

Other Identifiers

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PEG_study_ASD

Identifier Type: -

Identifier Source: org_study_id

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