MedPath

Evaluating the Alimentary and Respiratory Tracts in Health and Disease (EARTH) Research Program.

Conditions
Hirschprung's Disease
Obstructive Sleep Apnea
Cystic Fibrosis
Healthy
Registration Number
NCT04071314
Lead Sponsor
The University of New South Wales
Brief Summary

The investigators have established the "Evaluating the Alimentary and Respiratory Tracts in Health and disease" (EARTH) research program. It provides a structured approach to analysing gastrointestinal and respiratory microbiomes, along with diet and symptomatology, in children with a gastrointestinal and/or respiratory condition with recognised long-term morbidity (e.g. cystic fibrosis, obstructive sleep apnoea, or Hirschsprung's disease).

The EARTH program consists of a series of prospective, longitudinal, controlled, observational studies, with each individual study comparing children with a chronic gastrointestinal and/or respiratory condition to healthy controls (HC). It will be conducted in an Australian tertiary paediatric hospital (although the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared to age and gender matched HC across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) a stool sample, (ii) an oropharyngeal swab or sputum sample, (iii) a semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life, and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro- and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will also be compared between children with a condition and HC.

The investigators hypothesise that:

(i) Children with chronic gastrointestinal and/or respiratory conditions will have altered intestinal and respiratory microbiomes compared to healthy children, and (ii) Diet plays a key role in influencing the intestinal and respiratory microbiomes and this may impact on clinical outcomes, biomarkers of disease, and health-related quality of life.

Detailed Description

The objective of this research program is to evaluate and compare children with a chronic gastrointestinal and/or respiratory condition and age and gender matched HC. The primary objectives include analysing the intestinal and respiratory microbiomes (using an integrated "omics" approach) and dietary intake using validated, food frequency quetsionnaires. The secondary objectives include evaluating:

1. Known inflammatory biomarkers.

2. Symptomatology and health-related quality of life (HRQOL) using validated measures.

3. Phenotypic and clinical information.

4. Sociodemographic factors Additional secondary objectives include correlating within children with the same condition: (i) dietary intake with the intestinal microbiome; (ii) dietary intake with the respiratory microbiome; and (iii) the intestinal and respiratory microbiomes.

The investigators hypothesise that:

(i) Children with chronic gastrointestinal and/or respiratory conditions will have altered intestinal and respiratory microbiomes compared to healthy children, and (ii) Diet plays a key role in influencing the intestinal and respiratory microbiomes and this may impact on clinical outcomes, biomarkers of disease, and health-related quality of life.

To our knowledge, this program will enable the first series of studies comparing the intestinal and respiratory microbiomes and diet in children with chronic gastrointestinal and/or respiratory conditions. Initial results will be hypothesis-generating and used to direct future studies tailored to a specific focus or line of inquiry. Additionally, studies from this research program have potential for direct translation into clinical care as diet is a highly modifiable factor.

Study design. The EARTH program provides a framework for a series of prospective, longitudinal, controlled, observational studies, with each individual study comparing children with a chronic gastrointestinal and/or respiratory condition to HC. A single healthy control group will be used for comparison against all conditions. The standardised methodological approach will also allow for comparisons between different health conditions.

Procedures.

Each participant will be assessed on three occasions over a 12-month period; at study entry, 6- and 12-month follow-up. At each time-point, the following will be collected:

* A stool sample;

* An oropharyngeal swab or sputum sample (a sputum sample will be obtained in children able to expectorate and an oropharyngeal swab will be collected in children unable to expectorate);

* Dietary intake measured using the Australian Child and Adolescent Eating Survey (ACAES) (2 to 18 years) or 24-hour food recall (0 up to 2 years);

* A secure, password-protected online survey comprising:

i. PedsQL Infant Scales (0-2yr) \& Gastrointestinal Symptoms Module (2-18yr),41-43 tailored to age; ii. Rome IV Questionnaire (0 to 18 years); iii. Spence Children's Anxiety Scale (3 to 18 years); iv. Short Mood and Feelings Questionnaires (6 to 18 years); v. Clinical and biochemical results obtained through routine care and hospitalisations (if available); vi. Sociodemographic factors (baseline survey only);

* Anthropometrics: height, weight and BMI z-scores.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
72
Inclusion Criteria
  • Are aged between 0 and 18 years;
  • Have been diagnosed with a chronic gastrointestinal and/or respiratory condition defined by consensus diagnostic criteria; or
  • Are free of any chronic health condition (healthy control group); and
  • Have a parent(s)/carer(s) who provides informed consent, or are at least 16 years old and provide informed consent.
Exclusion Criteria
  • Children who have an unrelated coexisting chronic medical illness(es) associated with alterations in dietary intake or suspected alterations in the intestinal and/or respiratory microbiomes;
  • Inability to comply with study requirements;
  • Parent(s)/guardian(s) are unable to speak English or do not have a reading level age of at least 12 years.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
3A.i.12 Diet - total energy intakeChange from baseline at 12 months

Kilojoules (assessed using a 24-hour recall or ACAES).

3B.i.6 Diet - percentage energy from core foodsChange from baseline at 6 months

(assessed using a 24-hour recall or ACAES).

3B.i.12 Diet - percentage energy from core foodsChange from baseline at 12 months

(assessed using a 24-hour recall or ACAES).

3C.i.0 Diet - total macronutrients intakeBaseline

Grams (assessed using a 24-hour recall or ACAES).

1D.iv.0 Intestinal Microbiome (Viruses) - relative abundances of viruses.Baseline

ANCOM analysis (assessed metagenomic sequencing).

1A.ii.0 Intestinal Microbiome (Bacteria) - Shannon indexBaseline

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

1A.ii.6 Intestinal Microbiome (Bacteria) - Shannon indexChange from baseline at 6 months

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

1A.i.0 Intestinal Microbiome (Bacteria) - RichnessBaseline

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

1A.i.6 Intestinal Microbiome (Bacteria) - RichnessChange from baseline at 6 months

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

1A.i.12 Intestinal Microbiome (Bacteria) - RichnessChange from baseline at 12 months

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

1A.iii.6 Intestinal Microbiome (Bacteria) - UNIFRAC distances6 months

Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).

1A.iii.12 Intestinal Microbiome (Bacteria) - UNIFRAC distances12 months

Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).

1A.iv.0 Intestinal Microbiome (Bacteria) - relative abundances of bacteriaBaseline

ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).

1A.iv.6 Intestinal Microbiome (Bacteria) - relative abundances of bacteriaChange from baseline at 6 months

ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).

1A.iv.12 Intestinal Microbiome (Bacteria) - relative abundances of bacteriaChange from baseline at 12 months

ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).

1A.ii.12 Intestinal Microbiome (Bacteria) - Shannon indexChange from baseline at 12 months

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

1A.iii.0 Intestinal Microbiome (Bacteria) - UNIFRAC distancesBaseline

Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).

1B.i.0 Intestinal Microbiome (Proteome) - normalised abundances of proteinsBaseline

(assessed using LC-MS).

1B.i.6 Intestinal Microbiome (Proteome) - normalised abundances of proteinsChange from baseline at 6 months

(assessed using LC-MS).

1B.i.12 Intestinal Microbiome (Proteome) - normalised abundances of proteinsChange from baseline at 12 months

(assessed using LC-MS).

1C.i.0 Intestinal Microbiome (Metabolome) - normalised abundances of metabolitesBaseline

(assessed using LC-MS).

1D.i.0 Intestinal Microbiome (Viruses) - RichnessBaseline

Measurement of alpha diversity (assessed metagenomic sequencing).

1C.i.6 Intestinal Microbiome (Metabolome) - normalised abundances of metabolitesChange from baseline at 6 months

(assessed using LC-MS).

1C.i.12 Intestinal Microbiome (Metabolome) - normalised abundances of metabolitesChange from baseline at 12 months

(assessed using LC-MS).

1D.i.6 Intestinal Microbiome (Viruses) - RichnessChange from baseline at 6 months

Measurement of alpha diversity (assessed metagenomic sequencing).

1D.i.12 Intestinal Microbiome (Viruses) - RichnessChange from baseline at 12 months

Measurement of alpha diversity (assessed metagenomic sequencing).

1D.ii.6 Intestinal Microbiome (Viruses) - Shannon indexChange from baseline at 6 months

Measurement of alpha diversity (assessed metagenomic sequencing).

1D.ii.12 Intestinal Microbiome (Viruses) - Shannon indexChange from baseline at 12 months

Measurement of alpha diversity (assessed metagenomic sequencing).

1D.iii.0 Intestinal Microbiome (Viruses) - Bray-Curtis dissimilarityBaseline

Measurement of beta diversity (assessed metagenomic sequencing).

1D.ii.0 Intestinal Microbiome (Viruses) - Shannon indexBaseline

Measurement of alpha diversity (assessed metagenomic sequencing).

1D.iii.12 Intestinal Microbiome (Viruses) - Bray-Curtis dissimilarity12 months

Measurement of beta diversity (assessed metagenomic sequencing).

1D.iii.6 Intestinal Microbiome (Viruses) - Bray-Curtis dissimilarity6 months

Measurement of beta diversity (assessed metagenomic sequencing).

1D.iv.12 Intestinal Microbiome (Viruses) - relative abundances of viruses.Change from baseline at 12 months

ANCOM analysis (assessed metagenomic sequencing).

2A.i.6 Respiratory Microbiome (Bacteria) - RichnessChange from baseline at 6 months

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

1D.iv.6 Intestinal Microbiome (Viruses) - relative abundances of viruses.Change from baseline at 6 months

ANCOM analysis (assessed metagenomic sequencing).

2A.i.0 Respiratory Microbiome (Bacteria) - RichnessBaseline

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

2A.i.12 Respiratory Microbiome (Bacteria) - RichnessChange from baseline at 12 months

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

2A.ii.0 Respiratory Microbiome (Bacteria) - Shannon indexBaseline

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

2A.ii.6 Respiratory Microbiome (Bacteria) - Shannon indexChange from baseline at 6 months

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

2A.ii.12 Respiratory Microbiome (Bacteria) - Shannon indexChange from baseline at 12 months

Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).

2A.iii.12 Respiratory Microbiome (Bacteria) - UNIFRAC distancesChange from baseline at 12 months

Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).

2A.iii.0 Respiratory Microbiome (Bacteria) - UNIFRAC distancesBaseline

Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).

2A.iii.6 Respiratory Microbiome (Bacteria) - UNIFRAC distancesChange from baseline at 6 months

Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).

2A.iv.0 Respiratory Microbiome (Bacteria) - relative abundances of bacteriaBaseline

ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).

2B.i.0 Respiratory Microbiome (Proteome) - normalised abundances of proteinsBaseline

(assessed using LC-MS).

2A.iv.6 Respiratory Microbiome (Bacteria) - relative abundances of bacteriaChange from baseline at 6 months

ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).

2C.i.0 Respiratory Microbiome (Metabolome) - normalised abundances of metabolitesBaseline

(assessed using LC-MS).

2D.i.12 Respiratory Microbiome (Viruses) - RichnessChange from baseline at 12 months

Measurement of alpha diversity (assessed metagenomic sequencing).

2A.iv.12 Respiratory Microbiome (Bacteria) - relative abundances of bacteriaChange from baseline at 12 months

ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).

2B.i.6 Respiratory Microbiome (Proteome) - normalised abundances of proteinsChange from baseline at 6 months

(assessed using LC-MS).

2B.i.12 Respiratory Microbiome (Proteome) - normalised abundances of proteinsChange from baseline at 12 months

(assessed using LC-MS).

2C.i.6 Respiratory Microbiome (Metabolome) - normalised abundances of metabolitesChange from baseline at 6 months

(assessed using LC-MS).

2C.i.12 Respiratory Microbiome (Metabolome) - normalised abundances of metabolitesChange from baseline at 12 months

(assessed using LC-MS).

2D.i.0 Respiratory Microbiome (Viruses) - RichnessBaseline

Measurement of alpha diversity (assessed metagenomic sequencing).

2D.i.6 Respiratory Microbiome (Viruses) - RichnessChange from baseline at 6 months

Measurement of alpha diversity (assessed metagenomic sequencing).

2D.ii.0 Respiratory Microbiome (Viruses) - Shannon indexBaseline

Measurement of alpha diversity (assessed metagenomic sequencing).

2D.ii.6 Respiratory Microbiome (Viruses) - Shannon indexChange from baseline at 6 months

Measurement of alpha diversity (assessed metagenomic sequencing).

2D.ii.12 Respiratory Microbiome (Viruses) - Shannon indexChange from baseline at 12 months

Measurement of alpha diversity (assessed metagenomic sequencing).

2D.iii.0 Respiratory Microbiome (Viruses) - Bray-Curtis dissimilarityBaseline

Measurement of beta diversity (assessed metagenomic sequencing).

2D.iv.6 Respiratory Microbiome (Viruses) - relative abundances of virusesChange from baseline at 6 months

ANCOM analysis (assessed metagenomic sequencing).

2D.iv.0 Respiratory Microbiome (Viruses) - relative abundances of virusesBaseline

ANCOM analysis (assessed metagenomic sequencing).

3A.i.6 Diet - total energy intakeChange from baseline at 6 months

Kilojoules (assessed using a 24-hour recall or ACAES).

2D.iii.6 Respiratory Microbiome (Viruses) - Bray-Curtis dissimilarity6 months

Measurement of beta diversity (assessed metagenomic sequencing).

2D.iii.12 Respiratory Microbiome (Viruses) - Bray-Curtis dissimilarity12 months

Measurement of beta diversity (assessed metagenomic sequencing).

2D.iv.12 Respiratory Microbiome (Viruses) - relative abundances of virusesChange from baseline at 12 months

ANCOM analysis (assessed metagenomic sequencing).

3A.i.0 Diet - total energy intakeBaseline

Kilojoules (assessed using a 24-hour recall or ACAES).

3B.i.0 Diet - percentage energy from core foodsBaseline

(assessed using a 24-hour recall or ACAES).

3C.i.6 Diet - total macronutrients intakeChange from baseline at 6 months

Grams (assessed using a 24-hour recall or ACAES).

3C.ii.6 Diet - macronutrients proportion of total energy intakeChange from baseline at 6 months

Percentage (assessed using a 24-hour recall or ACAES).

3C.i.12 Diet - total macronutrients intakeChange from baseline at 12 months

Grams (assessed using a 24-hour recall or ACAES).

3C.ii.0 Diet - macronutrients proportion of total energy intakeBaseline

Percentage (assessed using a 24-hour recall or ACAES).

3C.ii.12 Diet - macronutrients proportion of total energy intakeChange from baseline at 12 months

Percentage (assessed using a 24-hour recall or ACAES).

3D.i.0 Diet - total micronutrients intakeBaseline

Milligrams (assessed using a 24-hour recall or ACAES).

3D.i.6 Diet - total micronutrients intakeChange from baseline at 6 months

Milligrams (assessed using a 24-hour recall or ACAES).

3D.i.12 Diet - total micronutrients intakeChange from baseline at 12 months

Milligrams (assessed using a 24-hour recall or ACAES).

3D.ii.0 Diet - micronutrients proportion of total energy intakeBaseline

Percentage (assessed using a 24-hour recall or ACAES).

3E.i.12 Diet - diet quality scoreChange from baseline at 12 months

Australia recommended food score. Maximum possible score of 73, higher is better (assessed using the ACAES only).

3D.ii.6 Diet - micronutrients proportion of total energy intakeChange from baseline at 6 months

Percentage (assessed using a 24-hour recall or ACAES).

3D.ii.12 Diet - micronutrients proportion of total energy intakeChange from baseline at 12 months

Percentage (assessed using a 24-hour recall or ACAES).

3E.i.6 Diet - diet quality scoreChange from baseline at 6 months

Australia recommended food score. Maximum possible score of 73, higher is better (assessed using the ACAES only).

3E.i.0 Diet - diet quality scoreBaseline

Australia recommended food score. Maximum possible score of 73, higher is better (assessed using the ACAES only).

Secondary Outcome Measures
NameTimeMethod
6A.ii.0 Phenotypic & Clinical Information - Length (ages 0 to 2 years)Baseline

Z-score.

6A.ii.12 Phenotypic & Clinical Information - Length (ages 0 to 2 years)Change from baseline at 12 months

Z-score.

6A.iii.0 Phenotypic & Clinical Information - Height (ages 2 to 20 years)Baseline

Z-score.

6A.iii.6 Phenotypic & Clinical Information - Height (ages 2 to 20 years)Change from baseline at 6 months

Z-score.

4A.iii.6 Faecal biomarkers - C-reactive proteinChange from baseline at 6 months

mg/L (assessed using an ELISA).

4A.i.12 Faecal biomarkers - calprotectinChange from baseline at 12 months

mg/kg (assessed using an ELISA).

4A.ii.6 Faecal biomarkers - M2 pyruvate kinaseChange from baseline at 6 months

U/mL (assessed using an ELISA).

4A.ii.12 Faecal biomarkers - M2 pyruvate kinaseChange from baseline at 12 months

U/mL (assessed using an ELISA).

4A.iii.12 Faecal biomarkers - C-reactive proteinChange from baseline at 12 months

mg/L (assessed using an ELISA).

4A.i.0 Faecal biomarkers - calprotectinBaseline

mg/kg (assessed using an ELISA).

4A.i.6 Faecal biomarkers - calprotectinChange from baseline at 6 months

mg/kg (assessed using an ELISA).

4A.ii.0 Faecal biomarkers - M2 pyruvate kinaseBaseline

U/mL (assessed using an ELISA).

4A.iii.0 Faecal biomarkers - C-reactive proteinBaseline

mg/L (assessed using an ELISA).

4A.iv.6 Faecal biomarkers - InterleukinsChange from baseline at 6 months

IU (assessed using an ELISA).

4A.iv.12 Faecal biomarkers - InterleukinsChange from baseline at 12 months

IU (assessed using an ELISA).

4B.i.6 Respiratory biomarkers - calprotectinChange from baseline at 6 months

mg/kg (assessed using an ELISA).

4A.iv.0 Faecal biomarkers - InterleukinsBaseline

IU (assessed using an ELISA).

4B.i.0 Respiratory biomarkers - calprotectinBaseline

mg/kg (assessed using an ELISA).

4B.i.12 Respiratory biomarkers - calprotectinChange from baseline at 12 months

mg/kg (assessed using an ELISA).

4B.ii.6 Respiratory biomarkers - C-reactive proteinChange from baseline at 6 months

mg/L (assessed using an ELISA).

4B.ii.0 Respiratory biomarkers - C-reactive proteinBaseline

mg/L (assessed using an ELISA).

4B.iii.6 Respiratory biomarkers - InterleukinsChange from baseline at 6 months

IU (assessed using an ELISA).

4B.iii.12 Respiratory biomarkers - InterleukinsChange from baseline at 12 months

IU (assessed using an ELISA).

5A.iii.12 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 5-7 years)Change from baseline at 12 months

Parent report for young children (ages 5-7 years) or young child report (ages 5-7 years). Score out of 100, higher scores indicate better HRQOL.

5A.iv.0 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 8-12 years)Baseline

Parent report for children (ages 8-12 years) or child report (ages 8-12 years). Score out of 100, higher scores indicate better HRQOL.

5A.v.12 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 13-18 years)Change from baseline at 12 months

Parent report for teens (ages 13-18 years) or teen report (ages 13-18 years). Score out of 100, higher scores indicate better HRQOL.

5B.i.0 Symptomatology & HRQOL - Rome IV Parent-Report Form for Infants and Toddlers (ages 0-3)Baseline

29 items for ages 0-12 months. 18 items for ages 1-3 years. Defined diagnostic criteria for functional gastrointestinal disorders in neonates and toddlers: Infant regurgitation, Infant rumination syndrome, Cyclic vomiting syndrome, Infant colic, Functional diarrhoea, Infant dyschezia, Functional constipation.

4B.ii.12 Respiratory biomarkers - C-reactive proteinChange from baseline at 12 months

mg/L (assessed using an ELISA).

4B.iii.0 Respiratory biomarkers - InterleukinsBaseline

IU (assessed using an ELISA).

5A.i.0 Symptomatology & HRQOL - PedsQL Infant Scales (ages 1-12 and 13-24 months)Baseline

Parent report for infants (ages 1-12 months) or (ages 13-24 months). Score out of 100, higher scores indicate better HRQOL.

5A.i.6 Symptomatology & HRQOL - PedsQL Infant Scales (ages 1-12 and 13-24 months)Change from baseline at 6 months

Parent report for infants (ages 1-12 months) or (ages 13-24 months). Score out of 100, higher scores indicate better HRQOL.

5A.iii.0 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 5-7 years)Baseline

Parent report for young children (ages 5-7 years) or young child report (ages 5-7 years). Score out of 100, higher scores indicate better HRQOL.

5A.i.12 Symptomatology & HRQOL - PedsQL Infant Scales (ages 1-12 and 13-24 months)Change from baseline at 12 months

Parent report for infants (ages 1-12 months) or (ages 13-24 months). Score out of 100, higher scores indicate better HRQOL.

5A.ii.0 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 2-4 years)Baseline

Parent report for toddlers (ages 2-4 years). Score out of 100, higher scores indicate better HRQOL.

5A.iii.6 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 5-7 years)Change from baseline at 6 months

Parent report for young children (ages 5-7 years) or young child report (ages 5-7 years). Score out of 100, higher scores indicate better HRQOL.

5A.ii.6 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 2-4 years)Change from baseline at 6 months

Parent report for toddlers (ages 2-4 years). Score out of 100, higher scores indicate better HRQOL.

5A.ii.12 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 2-4 years)Change from baseline at 12 months

Parent report for toddlers (ages 2-4 years). Score out of 100, higher scores indicate better HRQOL.

5A.iv.6 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 8-12 years)Change from baseline at 6 months

Parent report for children (ages 8-12 years) or child report (ages 8-12 years). Score out of 100, higher scores indicate better HRQOL.

5A.iv.12 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 8-12 years)Change from baseline at 12 months

Parent report for children (ages 8-12 years) or child report (ages 8-12 years). Score out of 100, higher scores indicate better HRQOL.

5A.v.0 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 13-18 years)Baseline

Parent report for teens (ages 13-18 years) or teen report (ages 13-18 years). Score out of 100, higher scores indicate better HRQOL.

5A.v.6 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 13-18 years)Change from baseline at 6 months

Parent report for teens (ages 13-18 years) or teen report (ages 13-18 years). Score out of 100, higher scores indicate better HRQOL.

5B.i.6 Symptomatology & HRQOL - Rome IV Parent-Report Form for Infants and Toddlers (ages 0-3)6 months

29 items for ages 0-12 months. 18 items for ages 1-3 years. Defined diagnostic criteria for functional gastrointestinal disorders in neonates and toddlers: Infant regurgitation, Infant rumination syndrome, Cyclic vomiting syndrome, Infant colic, Functional diarrhoea, Infant dyschezia, Functional constipation.

5D.i.6 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Parent Report on Child, ages 6-18 years).Change from baseline at 6 months

13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.

5B.i.12 Symptomatology & HRQOL - Rome IV Parent-Report Form for Infants and Toddlers (ages 0-3)12 months

29 items for ages 0-12 months. 18 items for ages 1-3 years. Defined diagnostic criteria for functional gastrointestinal disorders in neonates and toddlers: Infant regurgitation, Infant rumination syndrome, Cyclic vomiting syndrome, Infant colic, Functional diarrhoea, Infant dyschezia, Functional constipation.

5D.i.12 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Parent Report on Child, ages 6-18 years).Change from baseline at 12 months

13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.

5B.iii.0 Symptomatology & HRQOL - Rome IV Self-Report Form for Children and Adolescents (10 years of age and older)Baseline

42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.

5B.iii.6 Symptomatology & HRQOL - Rome IV Self-Report Form for Children and Adolescents (10 years of age and older)6 months

42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.

5B.iii.12 Symptomatology & HRQOL - Rome IV Self-Report Form for Children and Adolescents (10 years of age and older)12 months

42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.

5B.ii.0 Symptomatology & HRQOL - Rome IV Parent-Report Form for Children and Adolescents (4 years of age and older)Baseline

42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.

5D.ii.0 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Child Self Report, ages 6-18 years).Baseline

13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.

5B.ii.6 Symptomatology & HRQOL - Rome IV Parent-Report Form for Children and Adolescents (4 years of age and older)6 months

42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.

5B.ii.12 Symptomatology & HRQOL - Rome IV Parent-Report Form for Children and Adolescents (4 years of age and older)12 months

42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.

5C.ii.6 Symptomatology & HRQOL - Spence Children's Anxiety Scale (Parent report for 5 years and older)Change from baseline at 6 months

38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.

5C.i.0 Symptomatology & HRQOL - Spence Children's Anxiety Scale; Preschool Anxiety Scale (Parent report for ages 0 to 4)Baseline

34 items. Maximum possible scores of 112. A score 1 SD above mean for a subscale or total score warrants further clinical investigation. A score of 0.5 SD above the mean on total score is indicative of an elevated, but not clinical level of anxiety.

5C.i.12 Symptomatology & HRQOL - Spence Children's Anxiety Scale; Preschool Anxiety Scale (Parent report for ages 0 to 4)Change from baseline at 12 months

34 items. Maximum possible scores of 112. A score 1 SD above mean for a subscale or total score warrants further clinical investigation. A score of 0.5 SD above the mean on total score is indicative of an elevated, but not clinical level of anxiety.

5D.ii.6 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Child Self Report, ages 6-18 years).Change from baseline at 6 months

13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.

6A.i.0 Phenotypic & Clinical Information - Weight (ages 0 to 20 years)Baseline

Z-score.

6A.i.6 Phenotypic & Clinical Information - Weight (ages 0 to 20 years)Change from baseline at 6 months

Z-score.

5C.i.6 Symptomatology & HRQOL - Spence Children's Anxiety Scale; Preschool Anxiety Scale (Parent report for ages 0 to 4)Change from baseline at 6 months

34 items. Maximum possible scores of 112. A score 1 SD above mean for a subscale or total score warrants further clinical investigation. A score of 0.5 SD above the mean on total score is indicative of an elevated, but not clinical level of anxiety.

5C.ii.12 Symptomatology & HRQOL - Spence Children's Anxiety Scale (Parent report for 5 years and older)Change from baseline at 12 months

38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.

5C.iii.0 Symptomatology & HRQOL - Spence Children's Anxiety Scale (8 years and older)Baseline

38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.

5C.ii.0 Symptomatology & HRQOL - Spence Children's Anxiety Scale (Parent report for 5 years and older)Baseline

38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.

5C.iii.6 Symptomatology & HRQOL - Spence Children's Anxiety Scale (8 years and older)Change from baseline at 6 months

38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.

5C.iii.12 Symptomatology & HRQOL - Spence Children's Anxiety Scale (8 years and older)Change from baseline at 12 months

38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.

5D.i.0 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Parent Report on Child, ages 6-18 years).Baseline

13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.

5D.ii.12 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Child Self Report, ages 6-18 years).Change from baseline at 12 months

13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.

6A.i.12 Phenotypic & Clinical Information - Weight (ages 0 to 20 years)Change from baseline at 12 months

Z-score.

6A.ii.6 Phenotypic & Clinical Information - Length (ages 0 to 2 years)Change from baseline at 6 months

Z-score.

6A.iii.12 Phenotypic & Clinical Information - Height (ages 2 to 20 years)Change from baseline at 12 months

Z-score.

6A.iv.0 Phenotypic & Clinical Information - Weight-for-length (ages 0 to 2 years)Baseline

Z-score.

6A.iv.6 Phenotypic & Clinical Information - Weight-for-length (ages 0 to 2 years)Change from baseline at 6 months

Z-score.

6A.iv.12 Phenotypic & Clinical Information - Weight-for-length (ages 0 to 2 years)Change from baseline at 12 months

Z-score.

6A.v.12 Phenotypic & Clinical Information - Body mass index (ages 2 to 20 years)Change from baseline at 12 months

Z-score.

6B.iii.12 Phenotypic & Clinical Information - Number of emergency department presentations12 months

During period from baseline to 12 months.

6A.v.0 Phenotypic & Clinical Information - Body mass index (ages 2 to 20 years)Baseline

Z-score.

6A.v.6 Phenotypic & Clinical Information - Body mass index (ages 2 to 20 years)Change from baseline at 6 months

Z-score.

6B.i.6 Phenotypic & Clinical Information - Number of hospitalisations6 months

During period from baseline to 6 months.

6B.i.12 Phenotypic & Clinical Information - Number of hospitalisations12 months

During period from baseline to 12 months.

6B.ii.6 Phenotypic & Clinical Information - Length of hospitalisations6 months

Days hospitalised during period from baseline to 6 months.

6B.iii.6 Phenotypic & Clinical Information - Number of emergency department presentations6 months

During period from baseline to 6 months.

6B.ii.12 Phenotypic & Clinical Information - Length of hospitalisations12 months

Days hospitalised during period from baseline to 12 months.

Trial Locations

Locations (1)

Sydney Children's Hospital

🇦🇺

Randwick, New South Wales, Australia

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