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

NCT04071314 | Unknown

• 1 other identifier: HREC/18/SCHN/26
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis; Hirschprung's Disease; Obstructive Sleep Apnea; Healthy

Keywords

Microbiota; Gastrointestinal Microbiome; Diet; Signs and Symptoms; Quality of Life; Anxiety; Depression

Outcome Measures

Primary Outcomes (81)

• 1A.i.0 Intestinal Microbiome (Bacteria) - Richness

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

  Baseline

• 1A.i.6 Intestinal Microbiome (Bacteria) - Richness

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

  Change from baseline at 6 months

• 1A.i.12 Intestinal Microbiome (Bacteria) - Richness

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

  Change from baseline at 12 months

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

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

  Baseline

• 1A.ii.6 Intestinal Microbiome (Bacteria) - Shannon index

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

  Change from baseline at 6 months

• 1A.ii.12 Intestinal Microbiome (Bacteria) - Shannon index

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

  Change from baseline at 12 months

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

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

  Baseline

• 1A.iii.6 Intestinal Microbiome (Bacteria) - UNIFRAC distances

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

  6 months

• 1A.iii.12 Intestinal Microbiome (Bacteria) - UNIFRAC distances

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

  12 months

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

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

  Baseline

• 1A.iv.6 Intestinal Microbiome (Bacteria) - relative abundances of bacteria

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

  Change from baseline at 6 months

• 1A.iv.12 Intestinal Microbiome (Bacteria) - relative abundances of bacteria

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

  Change from baseline at 12 months

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

  (assessed using LC-MS).

  Baseline

• 1B.i.6 Intestinal Microbiome (Proteome) - normalised abundances of proteins

  (assessed using LC-MS).

  Change from baseline at 6 months

• 1B.i.12 Intestinal Microbiome (Proteome) - normalised abundances of proteins

  (assessed using LC-MS).

  Change from baseline at 12 months

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

  (assessed using LC-MS).

  Baseline

• 1C.i.6 Intestinal Microbiome (Metabolome) - normalised abundances of metabolites

  (assessed using LC-MS).

  Change from baseline at 6 months

• 1C.i.12 Intestinal Microbiome (Metabolome) - normalised abundances of metabolites

  (assessed using LC-MS).

  Change from baseline at 12 months

• 1D.i.0 Intestinal Microbiome (Viruses) - Richness

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Baseline

• 1D.i.6 Intestinal Microbiome (Viruses) - Richness

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Change from baseline at 6 months

• 1D.i.12 Intestinal Microbiome (Viruses) - Richness

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Change from baseline at 12 months

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

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Baseline

• 1D.ii.6 Intestinal Microbiome (Viruses) - Shannon index

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Change from baseline at 6 months

• 1D.ii.12 Intestinal Microbiome (Viruses) - Shannon index

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Change from baseline at 12 months

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

  Measurement of beta diversity (assessed metagenomic sequencing).

  Baseline

• 1D.iii.6 Intestinal Microbiome (Viruses) - Bray-Curtis dissimilarity

  Measurement of beta diversity (assessed metagenomic sequencing).

  6 months

• 1D.iii.12 Intestinal Microbiome (Viruses) - Bray-Curtis dissimilarity

  Measurement of beta diversity (assessed metagenomic sequencing).

  12 months

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

  ANCOM analysis (assessed metagenomic sequencing).

  Baseline

• 1D.iv.6 Intestinal Microbiome (Viruses) - relative abundances of viruses.

  ANCOM analysis (assessed metagenomic sequencing).

  Change from baseline at 6 months

• 1D.iv.12 Intestinal Microbiome (Viruses) - relative abundances of viruses.

  ANCOM analysis (assessed metagenomic sequencing).

  Change from baseline at 12 months

• 2A.i.0 Respiratory Microbiome (Bacteria) - Richness

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

  Baseline

• 2A.i.6 Respiratory Microbiome (Bacteria) - Richness

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

  Change from baseline at 6 months

• 2A.i.12 Respiratory Microbiome (Bacteria) - Richness

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

  Change from baseline at 12 months

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

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

  Baseline

• 2A.ii.6 Respiratory Microbiome (Bacteria) - Shannon index

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

  Change from baseline at 6 months

• 2A.ii.12 Respiratory Microbiome (Bacteria) - Shannon index

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

  Change from baseline at 12 months

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

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

  Baseline

• 2A.iii.6 Respiratory Microbiome (Bacteria) - UNIFRAC distances

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

  Change from baseline at 6 months

• 2A.iii.12 Respiratory Microbiome (Bacteria) - UNIFRAC distances

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

  Change from baseline at 12 months

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

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

  Baseline

• 2A.iv.6 Respiratory Microbiome (Bacteria) - relative abundances of bacteria

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

  Change from baseline at 6 months

• 2A.iv.12 Respiratory Microbiome (Bacteria) - relative abundances of bacteria

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

  Change from baseline at 12 months

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

  (assessed using LC-MS).

  Baseline

• 2B.i.6 Respiratory Microbiome (Proteome) - normalised abundances of proteins

  (assessed using LC-MS).

  Change from baseline at 6 months

• 2B.i.12 Respiratory Microbiome (Proteome) - normalised abundances of proteins

  (assessed using LC-MS).

  Change from baseline at 12 months

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

  (assessed using LC-MS).

  Baseline

• 2C.i.6 Respiratory Microbiome (Metabolome) - normalised abundances of metabolites

  (assessed using LC-MS).

  Change from baseline at 6 months

• 2C.i.12 Respiratory Microbiome (Metabolome) - normalised abundances of metabolites

  (assessed using LC-MS).

  Change from baseline at 12 months

• 2D.i.0 Respiratory Microbiome (Viruses) - Richness

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Baseline

• 2D.i.6 Respiratory Microbiome (Viruses) - Richness

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Change from baseline at 6 months

• 2D.i.12 Respiratory Microbiome (Viruses) - Richness

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Change from baseline at 12 months

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

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Baseline

• 2D.ii.6 Respiratory Microbiome (Viruses) - Shannon index

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Change from baseline at 6 months

• 2D.ii.12 Respiratory Microbiome (Viruses) - Shannon index

  Measurement of alpha diversity (assessed metagenomic sequencing).

  Change from baseline at 12 months

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

  Measurement of beta diversity (assessed metagenomic sequencing).

  Baseline

• 2D.iii.6 Respiratory Microbiome (Viruses) - Bray-Curtis dissimilarity

  Measurement of beta diversity (assessed metagenomic sequencing).

  6 months

• 2D.iii.12 Respiratory Microbiome (Viruses) - Bray-Curtis dissimilarity

  Measurement of beta diversity (assessed metagenomic sequencing).

  12 months

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

  ANCOM analysis (assessed metagenomic sequencing).

  Baseline

• 2D.iv.6 Respiratory Microbiome (Viruses) - relative abundances of viruses

  ANCOM analysis (assessed metagenomic sequencing).

  Change from baseline at 6 months

• 2D.iv.12 Respiratory Microbiome (Viruses) - relative abundances of viruses

  ANCOM analysis (assessed metagenomic sequencing).

  Change from baseline at 12 months

• 3A.i.0 Diet - total energy intake

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

  Baseline

• 3A.i.6 Diet - total energy intake

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

  Change from baseline at 6 months

• 3A.i.12 Diet - total energy intake

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

  Change from baseline at 12 months

• 3B.i.0 Diet - percentage energy from core foods

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

  Baseline

• 3B.i.6 Diet - percentage energy from core foods

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

  Change from baseline at 6 months

• 3B.i.12 Diet - percentage energy from core foods

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

  Change from baseline at 12 months

• 3C.i.0 Diet - total macronutrients intake

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

  Baseline

• 3C.i.6 Diet - total macronutrients intake

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

  Change from baseline at 6 months

• 3C.i.12 Diet - total macronutrients intake

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

  Change from baseline at 12 months

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

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

  Baseline

• 3C.ii.6 Diet - macronutrients proportion of total energy intake

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

  Change from baseline at 6 months

• 3C.ii.12 Diet - macronutrients proportion of total energy intake

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

  Change from baseline at 12 months

• 3D.i.0 Diet - total micronutrients intake

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

  Baseline

• 3D.i.6 Diet - total micronutrients intake

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

  Change from baseline at 6 months

• 3D.i.12 Diet - total micronutrients intake

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

  Change from baseline at 12 months

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

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

  Baseline

• 3D.ii.6 Diet - micronutrients proportion of total energy intake

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

  Change from baseline at 6 months

• 3D.ii.12 Diet - micronutrients proportion of total energy intake

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

  Change from baseline at 12 months

• 3E.i.0 Diet - diet quality score

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

  Baseline

• 3E.i.6 Diet - diet quality score

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

  Change from baseline at 6 months

• 3E.i.12 Diet - diet quality score

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

  Change from baseline at 12 months

Secondary Outcomes (81)

• 4A.i.0 Faecal biomarkers - calprotectin

  Baseline

• 4A.i.6 Faecal biomarkers - calprotectin

  Change from baseline at 6 months

• 4A.i.12 Faecal biomarkers - calprotectin

  Change from baseline at 12 months

• 4A.ii.0 Faecal biomarkers - M2 pyruvate kinase

  Baseline

• 4A.ii.6 Faecal biomarkers - M2 pyruvate kinase

  Change from baseline at 6 months

Study Arms (4)

Cystic fibrosis

Children diagnosed with cystic fibrosis. Children aged between 0 and 18 years.

Hirschsprung's disease

Children diagnosed with Hirschsprung's disease. Children aged between 0 and 18 years.

Obstructive sleep apnoea

Children diagnosed with obstructive sleep apnoea. Children aged between 0 and 18 years.

Healthy controls

Children free of any chronic health condition. Children aged between 0 and 18 years.

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Studies will be carried out at a single centre; the Sydney Children's Hospital (SCH) in Randwick, Australia. SCH is a tertiary paediatric hospital. Participants with chronic gastrointestinal and/or respiratory conditions will be approached at their routine clinic appointments in the outpatient department. Flyers will be placed in the hospital for recruitment of HC.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of New South Wales: lead

Study Sites (1)

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

RECRUITING

Related Publications (3)

• McKay I, van Dorst J, Katz T, Doumit M, Prentice B, Owens L, Belessis Y, Chuang S, Jaffe A, Thomas T, Coffey M, Ooi CY. Diet and the gut-lung axis in cystic fibrosis - direct & indirect links. Gut Microbes. 2023 Jan-Dec;15(1):2156254. doi: 10.1080/19490976.2022.2156254.

  PMID: 36573804 DERIVED

• Traini I, Chan SY, Menzies J, Hughes J, Coffey MJ, Katz T, McKay IR, Ooi CY, Leach ST, Krishnan U. Evaluating the Dietary Intake of Children With Esophageal Atresia: A Prospective, Controlled, Observational Study. J Pediatr Gastroenterol Nutr. 2022 Aug 1;75(2):221-226. doi: 10.1097/MPG.0000000000003498. Epub 2022 Jun 1.

  PMID: 35653431 DERIVED

• Coffey MJ, McKay IR, Doumit M, Chuang S, Adams S, Stelzer-Braid S, Waters SA, Kasparian NA, Thomas T, Jaffe A, Katz T, Ooi CY. Evaluating the Alimentary and Respiratory Tracts in Health and disease (EARTH) research programme: a protocol for prospective, longitudinal, controlled, observational studies in children with chronic disease at an Australian tertiary paediatric hospital. BMJ Open. 2020 Apr 14;10(4):e033916. doi: 10.1136/bmjopen-2019-033916.

  PMID: 32295774 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

* 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).

MeSH Terms

Conditions

Cystic Fibrosis; Sleep Apnea, Obstructive; Signs and Symptoms; Anxiety Disorders; Depression

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Michael J Coffey

  University of New South Wales

  PRINCIPAL INVESTIGATOR

• Chee (Keith) Y Ooi

  University of New South Wales

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael J Coffey

CONTACT

61293825574; michael.coffey@unsw.edu.au

Chee (Keith) Y Ooi

CONTACT

61293825512; keith.ooi@unsw.edu.au

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: August 28, 2019
• Study Start: April 18, 2018
• Primary Completion: March 13, 2023
• Study Completion: March 13, 2023
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)