Clinical trial NCT05424757: Polyethylene Glycol Safety in Children
Official title: Quantitative Analysis of Selected PEG 3350 Components and Metabolites in Children's Plasma and Urine
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Polyethylene Glycols
Children, Only
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Food and Drug Administration (FDA)
First posted: 2022-06-21
Enrollment: 158
Sex: ALL
Minimum age (years): 0
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study population will be selected from children cared for at The Children's Hospital of Philadelphia.

Brief summary: The primary objective is to measure levels of selected PEG 3350 components and metabolites in the blood and urine of children who are already taking PEG 3350 compared to children who are not taking PEG 3350.

Changes to medical therapy are not recommended as part of this study.

Detailed description: For subjects taking PEG 3350, blood and urine will be collected 1.5 to 4 hours after subjects take PEG 3350.

For subjects who are not taking PEG 3350, the same PEG 3350 components and metabolites will be measured in blood and urine.

PEG 3350 containing medicines from study subjects will be analyzed for the same PEG 3350 components and metabolites.

A stool specimen will be collected for future studies.

Additional data will be obtained from:

* Review of medical records.
* A brief questionnaire.
* Child Behavior Checklist (CBCL) from the Achenbach System of Empirically Based Assessment (for children more than 1.5 years old)
* Bayley-IV Social-Emotional Scale assessment (for children less than 1.5 years old)

Eligibility criteria: Group 1: Children who do not have bowel or nervous system disease, or neuropsychiatric symptoms.

Inclusion criteria:

Children less than 17 years old who have been taking PEG 3350 for at least one month.

Dose of PEG 3350 greater than or equal to 0.4 grams/kg/day currently recommended by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines (2). Preferences will be given to children taking at least 17 grams/day.

Normal Physical and neurological development for age. Weight and height percentiles ≥ 5% and ≤ 95% for age.

Exclusion criteria:

Children with underlying bowel problems that might be expected to increase bowel permeability (are included in group 2). In this group we will specifically exclude children with:

Diarrhea within the past month. Note that PEG 3350 may cause loose stool and this is often the intended therapeutic effect. Therefore, we will exclude children with presumed infectious diarrhea since this may alter gut permeability but will include children whose loose stool is attributed to PEG 3350. If loose or watery stool began after initiation of PEG 3350 or after an increase in PEG 3350 dose within prior 3 days, children may be enrolled for GROUP 1.

Children whose stool had a recognized diarrhea causing pathogen within the past 4 months will be excluded since the time required to repair epithelial lining is not clear. Enteric pathogens that would prevent enrollment include Salmonella, Shigella, Campylobacter, Yersinia, E. Coli (enterotoxigenic, enteropathogenic, enteraggregative, enterohemorrhagic), Clostridum difficile, Rotavirus, Norovirus, Astrovirus, and other known or suspected diarrhea causing organisms.

H. pylori infection since this causes a stomach inflammation. HIV infection since this may alter bowel permeability (17) and predispose to other types of infection Symptoms neurologic disease or dysfunction (since they will be enrolled in Group 3).

Group 2: Children with problems that might increase intestinal epithelial permeability.

Inclusion criteria:

Children less than 17 years old who have been taking PEG 3350 for at least one month.

Dose of PEG 3350 greater than or equal to 0.4 grams/kg/day currently recommended by the NASPGHAN and ESPGHAN guidelines (2). Preferences will be given to children taking at 17 grams/day.

c. Any of the following problems associated with increased bowel permeability:

* Weight ≤ 5% for age. Malnutrition is associated with increased intestinal permeability.
* Children who had a pathogen (see Group 1 Exclusion Criteria "A. b." for list of pathogens) isolated from their stool within the past month.
* Children with celiac disease who are untreated or began treatment within the past 3 months.
* Children with inflammatory bowel disease
* Children with Hirschsprung disease. This intestinal motility disorder predisposes to bowel injury called enterocolitis (18-20).
* Children with intestinal motility disorders other than Hirschsprung disease.

Exclusion criteria:

a. Children with neurologic or neuropsychiatric symptoms. These children will be enrolled in Group 3.

Group 3: Children with underlying neurologic disease or with neuropsychiatric disorders or symptoms.

Inclusion criteria:

Children less than 17 years old who have been taking PEG 3350 for at least one month.

Dose of PEG 3350 greater than or equal to 0.4 grams/kg/day currently recommended by the NASPGHAN and ESPGHAN guidelines (2). Preference will be given to children taking at least 17 grams/day.

Any of the following problems with the nervous system:

* Diagnosed with a disease that affects nervous system function before starting PEG 3350.
* Diagnosed with a disease that affects nervous system function after starting PEG 3350.
* Abnormal nervous system function without a specific diagnosis.
* Episodic nervous system dysfunction. This might include seizure disorder, metabolic disease, or mitochondrial disease.

Note: Included in Group 3 are children with cerebral palsy, neuronal migration defects, traumatic brain injury, hypoxic ischemic encephalopathy, seizure disorder, tics, migraine, clinical depression, anxiety disorder, obsessive-compulsive disorder, post-surgical brain injury, autism spectrum disorder as well as genetic defects that affect the nervous system (Cornelia de Lange, Rett Syndrome, Pelizaeus-Merzbacher disease, etc.).

Any weight and height (i.e., no exclusions based on growth percentiles). Abnormalities in any organ including the bowel are acceptable.

Exclusion criteria:

a. There are no specific exclusion criteria. This is important since this group may be at the highest risk for PEG 3350 side effects.

Group 4: Children who are not taking PEG 3350. We will enroll 75 children who are not taking PEG 3350. Inclusion and exclusion criteria for these children will be the same as those detailed above for children who are taking PEG 3350 except that they may not have taken PEG 3350 within the last month.

Enrollment targets for Groups 1, 2 and 3:

1. 15 children taking PEG 3350, age 0-6 years old (for each Group).
2. 6 children taking PEG 3350, age 7-12 years old (for each Group).
3. 4 children taking PEG 3350, age 13-17 years old (for each Group).
4. An equal number of children in each age group who are not taking PEG 3350.

Primary outcomes:
measure: PEG 3350 related molecules in plasma
timeFrame: 15 minutes
measure: PEG 3350 related molecules in urine
timeFrame: 10 minutes
measure: PEG 3350 related molecules in medicine samples
timeFrame: 5 minutes
measure: Neurobehavioral symptoms in children who are taking PEG 3350
timeFrame: 5 minutes
measure: Baseline neurobehavioral symptoms in children who are not taking PEG 3350
timeFrame: 5 minutes
measure: Assessment of current Child behavior (1.5 years to 18 years old)
timeFrame: 30 minutes
measure: Assessment of current Child behavior (< 1.5 years old)
timeFrame: 90 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Robert O Heuckeroth, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: