NCT02743663

Brief Summary

The study will ascertain the ability of preschool lung function tests to distinguish healthy children from those with wheeze, and to differentiate phenotypes of wheezy children (high and low risk for asthma as defined by API) in order to predict response to therapy, and to explore the correlation between preschool lung function test results and symptoms, in order to develop objective methods for monitoring asthma.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
121

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Jun 2014

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2014

Completed
1.6 years until next milestone

First Submitted

Initial submission to the registry

January 13, 2016

Completed
3 months until next milestone

First Posted

Study publicly available on registry

April 19, 2016

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2020

Completed
Last Updated

February 8, 2021

Status Verified

February 1, 2021

Enrollment Period

6.5 years

First QC Date

January 13, 2016

Last Update Submit

February 5, 2021

Conditions

Keywords

pediatriclung ventilation inhomogeneitypreschoolasthmawheeze

Outcome Measures

Primary Outcomes (1)

  • Change in Lung Clearance Index (LCI) in wheezing subjects.

    Determine whether a change in LCI value captured over a 3 month period distinguishes two groups of wheezing children (high vs. low risk for asthma) as determined by the asthma predictive index (API).

    baseline and 3 months

Secondary Outcomes (11)

  • Obstructive Sleep Apnea (OSA)

    Day 1, and again 3 months later.

  • Change in asthma symptoms

    baseline and 3 months

  • Change in Forced Oscillation Technique (FOT) values in wheezing subjects.

    baseline and 3 months

  • Change in spirometry values in wheezing subjects.

    baseline and 3 months

  • Comparison of LCI values between wheezy subjects and healthy controls.

    Day 1 for wheezing subjects and healthy controls, and again 3 months later for wheezing subjects.

  • +6 more secondary outcomes

Study Arms (2)

Wheezing subjects

Two study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.

Procedure: Bronchodilator responseProcedure: Allergy Skin TestProcedure: Multiple-Breath WashoutProcedure: Forced Oscillation TechniqueProcedure: SpirometryDrug: salbutamolProcedure: Nasal BrushProcedure: Blood sampleProcedure: Basophil activation testProcedure: Nasal swab

Healthy cohort

One study visit will be completed with healthy participants. At this visit, three breathing tests will be performed: multiple-breath washout, forced oscillation technique, and spirometry. As well, an allergy skin test will be performed at the visit.

Procedure: Allergy Skin TestProcedure: Multiple-Breath WashoutProcedure: Forced Oscillation TechniqueProcedure: Spirometry

Interventions

Bronchodilator (Salbutamol - dose dependent on participant prescription) to wheezing subjects. 15 minutes after bronchodilator, spirometry and FOT repeated.

Wheezing subjects

Child will be tested for allergies to 17 different allergens, and positive (histamine) and negative (glycerin) controls, for a total of 19 allergens.

Healthy cohortWheezing subjects

Facemask in children 3-5 yrs, Wash-in phase: medical air inhaled during tidal breathing until steady state. Bias flow switched to 100% oxygen. Wash-out phase: patient breathes in 100% oxygen until nitrogen levels reach \~2%. Each test in duplicate and average is calculated.

Also known as: MBW
Healthy cohortWheezing subjects

Sterile mouthpiece attached to FOT device. Patient is tested seated with noseclips and mouthpiece. FOT device produces oscillations at different frequencies (from that flow into lungs. Device measures resistance and reactance in lungs.

Also known as: FOT
Healthy cohortWheezing subjects
SpirometryPROCEDURE

Forced exhale manoeuvre completed by participant into flow meter, measuring forced exhale volumes and speed.

Healthy cohortWheezing subjects

Given during bronchodilator response.

Also known as: ventolin
Wheezing subjects
Nasal BrushPROCEDURE

Nasal brush of 1 inferior turbinate to collect epithelial cells. Collected on either nare, choice dependent on how clear the nare is (i.e. no mucous, no nasal mucosal edema, no major structural impediments).

Wheezing subjects
Blood samplePROCEDURE

8mLs of venous blood collected using a butterfly needle of appropriate gauge. Blood sample used to collect CBC values, total IgE, serum, DNA, plasma, and whole blood.

Wheezing subjects

Collect basophils from whole blood sample, and expose cells to food allergens in flow cytometry machine to measure allergic response, if any.

Also known as: BAT
Wheezing subjects
Nasal swabPROCEDURE

Gentle swabbing of both nasal openings to collect mucous sample for analysis of microbial contents (i.e. bacteria, virus, fungi).

Wheezing subjects

Eligibility Criteria

Age3 Years - 5 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)
Sampling MethodNon-Probability Sample
Study Population

Wheezing preschool-aged subjects will be recruited within 5 days of their discharge from the Emergency Department at the Hospital for Sick Children. Healthy preschool-aged controls will be recruited from the community (concurrent observational studies being conducted by the PI at the Hospital for Sick Children, children of co-workers)

You may qualify if:

  • to 5 years of age (36 to 71 months)
  • Diagnosis of Asthma made by a physician in the emergency department
  • History of at least two other wheezing episode within the previous 12 months
  • Received salbutamol within 4hrs before emergency department visit, during current emergency department visit, or was prescribed salbutamol at discharge from emergency department.
  • to 5 years of age (36 to 71 months)
  • Free of a respiratory infection for a minimum of 4 weeks prior to the testing visit

You may not qualify if:

  • History or coexistence of renal, chronic pulmonary, cardiac, neurological or systemic disease
  • Born pre-term (\< 35 weeks GA)
  • Insufficient command of the English language

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood samples collected and divided into DNA pellet, plasma, serum, and whole blood. Small portion of sample sent for Total IgE and CBC. The eosinophil and IgE information will be used to assist with categorizing wheezy subjects into API categories. The DNA sample will be analyzed using genome-wide association studies (GWAS), and looking for single-nucleotide polymorphism (SNPs) that are known to be associated with asthma. The whole blood samples will be used for the basophil activation test; Urine samples; Nasal swab samples; Nasal brush samples;

MeSH Terms

Conditions

AsthmaRespiratory SoundsSleep Apnea, ObstructiveFood HypersensitivityVirus Diseases

Interventions

Skin TestsAlbuterolBlood Specimen CollectionBasophil Degranulation Test

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System DiseasesSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and SymptomsSleep Apnea SyndromesApneaRespiration DisordersSleep Disorders, IntrinsicDyssomniasSleep Wake DisordersNervous System DiseasesInfections

Intervention Hierarchy (Ancestors)

Immunologic TestsClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative TechniquesImmunologic TechniquesEthanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsAminesPhenethylaminesEthylaminesSpecimen HandlingPuncturesSurgical Procedures, Operative

Study Officials

  • Padmaja Subbarao, MD

    The Hospital for Sick Children

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Staff Respirologist

Study Record Dates

First Submitted

January 13, 2016

First Posted

April 19, 2016

Study Start

June 1, 2014

Primary Completion

December 1, 2020

Study Completion

December 1, 2020

Last Updated

February 8, 2021

Record last verified: 2021-02

Locations