Airway Inflammation in Congenital Diaphragmatic Hernia Patients

• Sponsor: The Hospital for Sick Children (Other)
• Overall Status: Completed
• CT.gov ID: NCT02453750
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arm: 1
• Duration (Months): 20
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

We propose to examine Congenital Diaphragmatic Hernia (CDH) patients for evidence of airway inflammation as a first step to characterize the reported bronchodilator responsiveness. Airway biopsy studies are invasive and thus we propose to perform induced sputum studies to document the amount and type of inflammation present. Another ancillary non-invasive measure of airway inflammation that we will use is exhaled nitric oxide (NO). The primary objective of this study is to determine if CDH patients have any evidence of airway inflammation. The hypothesis of this study is that children with CDH do not have evidence of airway inflammation associated with bronchodilator responsiveness. Based on this information, treatment for CDH patients will hopefully be more accurate and appropriate for their specific needs.

Condition or Disease	Intervention/Treatment	Phase
Congenital Diaphragmatic Hernia	Drug: Hypersaline; Drug: Bronchodilator Response	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Investigation of Airway Inflammation in Congenital Diaphragmatic Hernia Patients
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Hypersaline and Bronchodilator Response After the subject has performed post-bronchodilator spirometry, they will inhale 5 mls of 3% hypertonic saline for 7 minutes by nebulizer.

Drug: Hypersaline; Subject will inhale 5 mls of 3% hypertonic saline for 7 minutes by nebulizer. Sputum production (with cough) will be attempted post inhalation. A maximum of 3 hypertonic saline inhalations will be attempted if inhalation does not generate a productive cough. If sputum induction is not successful and the FEV1 falls <10%, the concentration of inhaled hypertonic saline will increase from 3 to 4%. If 5 mls of 4% hypertonic saline inhaled for 7 minutes does not produce a productive cough we will proceed to 5%. If 5 mls of 5% hypertonic saline inhaled for 7 minutes does not produce a productive cough the test is complete and the sample is labelled 'no sputum collected'. If FEV1 falls >10%, the previous step will be repeated.; Drug: Bronchodilator Response; A bronchodilator (Salbutamol 200 mcg or 2 puffs inhaled via spacer device) will be administered to all subjects in the pulmonary function laboratory. 15 minutes after administration of the bronchodilator spirometry will be repeated. This is performed routinely in CDH clinic and is not an additional test for this study.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Elevated Sputum Eosinophils [post sputum induction]

   Number of participants with sputum eosinophils greater than 3% percent of cells in the sputum

Secondary Outcome Measures

1. Number of Participant With Elevated Sputum Neutrophils [Baseline, +30 minutes]

   Elevation is defined as sputum neutrophils > or = 61% neutrophils = neutrophilic inflammation

2. Number of Participant With Elevated Exhaled Nitric Oxide (NO) Level [30 min]

   exhaled NO measurements will be performed according to the American Thoracic Society and European Respiratory Society guidelines. These tests are performed routinely as part of the respiratory evaluation of these patients and are not additional tests added for this study. greater than 20 ppb was considered elevated

3. Number of Participant With Bronchodilator Response [life time of child (age 6 to present age)]

   defined as a = or > 12% change in FEV1 post bronchodilator

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 6 - 18 years of age at enrolment

• Clinically stable at enrolment

• Attending follow-up in the CDH Clinic at SickKids

Exclusion Criteria:

• Unable to perform pulmonary function testing

• Clinically unstable at enrolment

• Known hypersensitivity to salbutamol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8

Sponsors and Collaborators

• The Hospital for Sick Children

Investigators

• Principal Investigator: Theo Moraes, MD, The Hospital for Sick Children

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Theo Moraes, Staff Respirologist, The Hospital for Sick Children
• ClinicalTrials.gov Identifier: NCT02453750
• Other Study ID Numbers: 1000028032
• First Posted: May 25, 2015
• Last Update Posted: Jan 31, 2019
• Last Verified: Aug 1, 2018

• Keywords provided by Theo Moraes, Staff Respirologist, The Hospital for Sick Children: Congenital Diaphragmatic Hernia; Airway Inflammation; Asthma; Hypersaline; Pediatrics
• Additional relevant MeSH terms: Hernias, Diaphragmatic, Congenital; Inflammation; Hernia; Hernia, Diaphragmatic; Bronchodilator Agents

Study Results

Participant Flow

Arm/Group Title	Hypersaline and Bronchodilator Response
Arm/Group Description	Each child will perform a sputum induction to obtain cells for analysis.
Period Title: Overall Study
STARTED	21
COMPLETED	21
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Hypersaline and Bronchodilator Response
Arm/Group Description	After the subject has performed post-bronchodilator spirometry, they will inhale 5 mls of 3% hypertonic saline for 7 minutes by nebulizer to obtain cells for analysis.
Overall Participants	21
Age (Count of Participants)
<=18 years	21 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	7 33.3%
Male	14 66.7%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Elevated Sputum Eosinophils
Description	Number of participants with sputum eosinophils greater than 3% percent of cells in the sputum
Time Frame	post sputum induction

Outcome Measure Data

Analysis Population Description

15 gave reasonable sputum for analysis, none had elevated sputum eosinophils

Arm/Group Title	Hypersaline and Bronchodilator Response
Arm/Group Description	everyone performs sputum induction
Measure Participants	15
Number [participants]	0 0%

2. Secondary Outcome

Title	Number of Participant With Elevated Sputum Neutrophils
Description	Elevation is defined as sputum neutrophils > or = 61% neutrophils = neutrophilic inflammation
Time Frame	Baseline, +30 minutes

Outcome Measure Data

Analysis Population Description

15 gave reasonable sputum

Arm/Group Title	Hypersaline and Bronchodilator Response
Arm/Group Description	After the subject has performed post-bronchodilator spirometry, they will inhale 5 mls of 3% hypertonic saline for 7 minutes by nebulizer.
Measure Participants	15
Number [participants]	0 0%

3. Secondary Outcome

Title	Number of Participant With Elevated Exhaled Nitric Oxide (NO) Level
Description	exhaled NO measurements will be performed according to the American Thoracic Society and European Respiratory Society guidelines. These tests are performed routinely as part of the respiratory evaluation of these patients and are not additional tests added for this study. greater than 20 ppb was considered elevated
Time Frame	30 min

Outcome Measure Data

Analysis Population Description

only 12 performed eNO

Arm/Group Title	Hypersaline and Bronchodilator Response
Arm/Group Description	eNO measured
Measure Participants	12
Count of Participants [Participants]	2 9.5%

4. Secondary Outcome

Title	Number of Participant With Bronchodilator Response
Description	defined as a = or > 12% change in FEV1 post bronchodilator
Time Frame	life time of child (age 6 to present age)

Outcome Measure Data

Analysis Population Description

all subjects performed PFTs

Arm/Group Title	Hypersaline and Bronchodilator Response
Arm/Group Description	spiro performed at start of visit
Measure Participants	21
Number [participants]	15 71.4%

Adverse Events

Arm/Group Title	Hypersaline and Bronchodilator Response
Arm/Group Description	After the subject has performed post-bronchodilator spirometry, they will inhale 5 mls of 3% hypertonic saline for 7 minutes by nebulizer.
All Cause Mortality
	Hypersaline and Bronchodilator Response
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Serious Adverse Events
	Hypersaline and Bronchodilator Response
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Other (Not Including Serious) Adverse Events
	Hypersaline and Bronchodilator Response
	Affected / at Risk (%)	# Events
Total	0/21 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.