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

NCT05025553 | Completed

• 1 other identifier: PEG_study_ASD
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Autistic Spectrum Disorder; Constipation

Keywords

Autism; 4-cresol; anxiety; autism spectrum disorder; biomarkers; constipation; microbiota

Outcome Measures

Primary Outcomes (6)

• Change in stool quality

  Stool quality was assessed by parental report using the Bristol Stool Scale (score ranges from 1 to 7, where 1 is "lumpy constipation" and 7 is "liquid diarrhoea").

  At baseline (T0) prior to gut mobilization; 1 month (T1) and 6 months (T2) after gut mobilization

• Change from baseline urinary concentrations of total p-cresol

  Urinary concentrations of total p-cresol, encompassing on average 95% p-cresylsulfate, 3%-4% p-cresylglucuronide and 0.5%-1% of unconjugated free p-cresol, were measured by HPLC three times, averaged and normalized by urinary specific gravity.

  First-morning urines were collected at home by parents at baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization

• Change in Childhood Autism Rating Scale (CARS)

  The Childhood Autism Rating Scale is a clinical rating scale for the trained clinician to rate the presence and severity of signs and symptoms of ASD by direct observation of the child. Scores can range from 15 to 60: below 30, non autistic; 30-36.5 mild to moderate autism; 37-60, severe autism

  At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization

• Change in Repetitive Behavior Scale-Revised (RBS-R)

  44- item questionnaire used to assess repetitive behaviors. Scores range from 0 to 3 (0 = the behavior does not occur, 3 = the behavior is present and severe). Overall rating (last question) ranges from 0 to 100, indicating that the set of behaviors described in the questionnaire do not represent a problem at all (0) or instead represent an extremely severe problem (100).

  At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization

• Change in Conners' Parent Rating Scale - Revised (CPRS-R)

  48-item rating scale used to evaluate through parental reports the presence of childhood hyperactivity/inattention, impulsivity and externalizing behaviors (scores for each item range from 0="not true, never, rarely" to 4="very true, very often or very frequent"; diagnostic threshold score = 60).

  At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization

• Change in Social Responsiveness Scale (SRS)

  65-item questionnaire used to assess social impairment, communication deficits and repetitive behaviors (T scores: \<60, normal range; 60-65, mild deficits; 66-75, moderate deficits; 76 or above, severe deficits in reciprocal social behavior).

  At baseline (T0), 1 month (T1) and 6 months (T2) after gut mobilization

Study Arms (1)

Gut mobilization

OTHER

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

Dietary Supplement: Gut mobilization

Interventions

Gut mobilization 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.

Gut mobilization

Eligibility Criteria

• Age: 2 Years - 8 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• ASD constipated children already treated with laxatives

Sponsors & Collaborators

• University of Messina: lead

Study Sites (1)

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

Messina, ME, I-98125, Italy

Location

Related Publications (11)

• 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.

  PMID: 22511450 BACKGROUND

• 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.

  PMID: 3607034 BACKGROUND

• 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.

  PMID: 33087514 BACKGROUND

• 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.

  PMID: 23380084 BACKGROUND

• 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.

  PMID: 21329489 BACKGROUND

• 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.

  PMID: 24130822 BACKGROUND

• 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.

  PMID: 26437875 BACKGROUND

• 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.

  PMID: 25010144 BACKGROUND

• 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.

  PMID: 32294927 BACKGROUND

• 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.

  PMID: 33857522 BACKGROUND

• 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.

  PMID: 27904735 RESULT

MeSH Terms

Conditions

Autism Spectrum Disorder; Constipation; Autistic Disorder; Anxiety Disorders

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor in Child & Adolescent Neuropsychiatry

Model Details: 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

Study Record Dates

• First Submitted: August 15, 2021
• First Posted: August 27, 2021
• Study Start: January 1, 2018
• Primary Completion: January 1, 2021
• Study Completion: February 1, 2021
• Last Updated: August 27, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)