Utilizing Exhaled Breathe Condensate Collection to Study Ion Regulation in Cystic Fibrosis

• Sponsor: University of Arizona (Other)
• Overall Status: Completed
• CT.gov ID: NCT01880723
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 32
• Location: 1
• Arms: 2
• Duration (Months): 44.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Our aims were to determine if exhaled breath condensate (EBC) could detect differences in ion regulation between cystic fibrosis (CF) and healthy and measure the effect of the albuterol on EBC ions in these populations. We hypothesized EBC chloride and sodium would be lower in CF patients at baseline and that albuterol would decrease EBC sodium and increase EBC chloride.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis; Healthy	Drug: Albuterol; Drug: Placebo saline	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Modifying Genes in Cystic Fibrosis: The Beta-2 Adrenergic Receptors and Epithelial Na+ Channels
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Albuterol 2.5 mg diluted in 3mL normal saline nebulized using a Power Neb2 nebulizer	Drug: Albuterol; 2.5 mg diluted in 3mL normal saline nebulized using a Power Neb2 nebulizer
Placebo Comparator: Saline (healthy only) nebulized 3 ml normal saline using a Power Neb2 nebulizer	Drug: Placebo saline; nebulized 3mL normal saline) using a Power Neb2 nebulizer

Outcome Measures

Primary Outcome Measures

1. Exhaled Sodium (mmol/L) [up to 90-minutes post albuterol]

   We collected exhaled breath condensate (EBC) samples, with subjects breathing on a Jaeger EcoScreen for 20 minutes. EBC samples were collected in cystic fibrosis and healthy subjects before and 30-, 60-, and 90-minutes following albuterol administration.

2. Net Exhaled Chloride [baseline to 90 minutes post albuterol administration]

   The calculation of net chloride efflux was used to account for the paracellular reabsorption of Cl- that will follow the reabsorption of Na+ to maintain electroneutral ion flux. Thus, the net chloride efflux calculation used was the gross chloride concentration plus the absolute value of the percent change in sodium from baseline multiplied by the gross chloride concentration for each time point: Net Cl- efflux - [Cl- X-min post] + (([Na+ X-min post]-[Na+Baseline])/ [Na+Baseline]) x [Cl- X-min post])

Secondary Outcome Measures

1. Diffusion Capacity of the Lungs for Carbon Monoxide [baseline, 30-, 60- and 90-minutes post albuterol administration]

   Using the rebreathe technique the diffusion capacity of the lungs for carbon monoxide and nitric oxide were measured, and this allowed for the determination of alveolar-capillary membrane conductance and pulmonary capillary blood volume. These measurements were made at baseline and 30-, 60- and 90-minutes post albuterol administration in cystic fibrosis and healthy subjects.

2. Diffusion Capacity of the Lungs for Nitric Oxide [baseline, 30-, 60- and 90-minutes post albuterol administration]

   Using the rebreathe technique the diffusion capacity of the lungs for carbon monoxide and nitric oxide were measured, and this allowed for the determination of alveolar-capillary membrane conductance and pulmonary capillary blood volume. These measurements were made at baseline and 30-, 60- and 90-minutes post albuterol administration in cystic fibrosis and healthy subjects.

3. Peripheral Oxygen Saturation [baseline, 30-, 60- and 90-minutes post albuterol]

   A finger pulse oximeter allowed for the measurement of peripheral oxygen saturation at baseline, 30-, 60- and 90-minutes post albuterol in cystic fibrosis and healthy subjects.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Healthy subjects:

• no cardiovascular abnormalities

• not overweight BMI>25

• 18-55 years of age

CF subjects:

• mild to moderate CF (FEV1>40% predicted)

• clinically diagnosed with positive sweat test (sweat Cl->60mmol/L)

• 10-55 years of age

• clinically stable

Exclusion Criteria:

Healthy subjects will be excluded if:

• If unable to consent for him/herself (cognitive impairment)

• Have a history or evidence of cardiovascular and/or pulmonary abnormalities.

• Have an abnormal 12-lead EKG

• Have an abnormal pulmonary function test

• Have a history of asthma

• Have a history of renal disease or estimated creatinine clearance < 55ml/min

• Women who are pregnant or planning to become pregnant during the study

CF subjects:

• If unable to consent for him/herself (cognitive impairment)

• Physically unable to perform exercise or breathing tests

• Have a history of renal disease or estimated creatinine clearance < 55ml/min

• Women who are pregnant or planning to become pregnant during the study.

• Have an abnormal 12-lead EKG

• Cystic Fibrosis related diabetes is uncontrolled

• Forced Expiratory Volume after 1 second (FEV1) is less than 40% predicted

• Have a history of joint disease

• Have history of pulmonary exacerbation within the last two weeks

• Experienced pulmonary hemorrhage within 6 months resulting in greater than 50cc of blood in the sputum

• not currently enrolled in any other research study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Pharmacy Practice and Science, University of Arizona, Tucson, Arizona	Tucson	Arizona	United States	85721

Sponsors and Collaborators

• University of Arizona
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Wayne J Morgan, MD, Department of Pediatrics- Pulmonology, Allergy and Immunology, University of Arizona, Tucson, Arizona
• Principal Investigator: Cori M Daines, MD, Department of Pediatrics- Pulmonology, Allergy and Immunology, University of Arizona, Tucson, Arizona
• Principal Investigator: Eric M Snyder, PhD, Department of Pharmacy Practice and Science, University of Arizona, Tucson, Arizona
• Principal Investigator: Hanna Phan, PharmD, Department of Pharmacy Practice and Science, University of Arizona, Tucson, Arizona
• Principal Investigator: Asad Patanwalla, PharmD, Department of Pharmacy Practice and Science, University of Arizona, Tucson, Arizona

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Courtney Wheatley, Graduate Research Assistant, University of Arizona
• ClinicalTrials.gov Identifier: NCT01880723
• Other Study ID Numbers: 08-1123-01; 1R01HL108962-01
• First Posted: Jun 19, 2013
• Last Update Posted: Jun 25, 2014
• Last Verified: May 1, 2014

• Keywords provided by Courtney Wheatley, Graduate Research Assistant, University of Arizona: exhaled breath condensate; diffusion capacity of the lungs for carbon monoxide and nitric oxide; albuterol; peripheral oxygen saturation; ion regulation
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Albuterol

Study Results

Participant Flow

Arm/Group Title	Healthy	Cystic Fibrosis
Arm/Group Description	Healthy control subjects	Patients diagnosed with cystic fibrosis
Period Title: Overall Study
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Healthy	Cystic Fibrosis	Total
Arm/Group Description	Healthy Control subjects	Patients diagnosed with cystic fibrosis	Total of all reporting groups
Overall Participants	16	16	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25 (6)	22 (8)	24 (7)
Sex: Female, Male (Count of Participants)
Female	8 50%	4 25%	12 37.5%
Male	8 50%	12 75%	20 62.5%
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	64 (9)	60 (9)	62 (9)
Height (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	169 (8)	166 (8)	167 (8)
BMI (kg/m2) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	23 (3)	22 (3)	22 (3)
BSA (m2) (m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m2]	1.7 (0.1)	1.7 (0.2)	1.7 (0.1)
VO2 peak (% predicted) (percent predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent predicted]	108 (35)	54 (24)	85 (39)

Outcome Measures

1. Primary Outcome

Title	Exhaled Sodium (mmol/L)
Description	We collected exhaled breath condensate (EBC) samples, with subjects breathing on a Jaeger EcoScreen for 20 minutes. EBC samples were collected in cystic fibrosis and healthy subjects before and 30-, 60-, and 90-minutes following albuterol administration.
Time Frame	up to 90-minutes post albuterol

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy	Cystic Fibrosis
Arm/Group Description	Healthy control subjects	Patients diagnosed with cystic fibrosis
Measure Participants	16	16
Baseline	2.58 (1.51)	2.24 (1.09)
30 minutes post	1.97 (0.58)	2.11 (0.93)
60 minutes post	2.37 (0.94)	1.73 (0.85)
90 minutes post	2.23 (1.34)	1.86 (0.93)

2. Secondary Outcome

Title	Diffusion Capacity of the Lungs for Carbon Monoxide
Description	Using the rebreathe technique the diffusion capacity of the lungs for carbon monoxide and nitric oxide were measured, and this allowed for the determination of alveolar-capillary membrane conductance and pulmonary capillary blood volume. These measurements were made at baseline and 30-, 60- and 90-minutes post albuterol administration in cystic fibrosis and healthy subjects.
Time Frame	baseline, 30-, 60- and 90-minutes post albuterol administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy	Cystic Fibrosis
Arm/Group Description	Healthy control subjects	Patients diagnosed with cystic fibrosis
Measure Participants	16	16
Baseline	21.5 (5.8)	17.3 (4.4)
30 minutes post	21.6 (5.3)	17.4 (4.3)
60 minutes post	21.6 (6.2)	17.0 (4.4)
90 minutes post	21.2 (5.5)	17.1 (4.9)

3. Secondary Outcome

Title	Diffusion Capacity of the Lungs for Nitric Oxide
Description	Using the rebreathe technique the diffusion capacity of the lungs for carbon monoxide and nitric oxide were measured, and this allowed for the determination of alveolar-capillary membrane conductance and pulmonary capillary blood volume. These measurements were made at baseline and 30-, 60- and 90-minutes post albuterol administration in cystic fibrosis and healthy subjects.
Time Frame	baseline, 30-, 60- and 90-minutes post albuterol administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy	Cystic Fibrosis
Arm/Group Description	Healthy control subjects	Patients diagnosed with cystic fibrosis
Measure Participants	16	16
Baseline	70.3 (18.9)	55.0 (15.0)
30 minutes post	70.8 (16.7)	56.4 (15.0)
60 minutes post	72.1 (19.2)	56.2 (16.6)
90 minutes post	73.0 (20.6)	58.5 (17.8)

4. Primary Outcome

Title	Net Exhaled Chloride
Description	The calculation of net chloride efflux was used to account for the paracellular reabsorption of Cl- that will follow the reabsorption of Na+ to maintain electroneutral ion flux. Thus, the net chloride efflux calculation used was the gross chloride concentration plus the absolute value of the percent change in sodium from baseline multiplied by the gross chloride concentration for each time point: Net Cl- efflux - [Cl- X-min post] + (([Na+ X-min post]-[Na+Baseline])/ [Na+Baseline]) x [Cl- X-min post])
Time Frame	baseline to 90 minutes post albuterol administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy	Cystic Fibrosis
Arm/Group Description	Healthy control subjects	Patients diagnosed with cystic fibrosis
Measure Participants	16	16
Baseline	0.064 (0.05)	0.037 (0.02)
30 minutes post	0.078 (0.143)	0.048 (0.031)
60 minutes post	0.084 (0.073)	0.057 (0.038)
90 minutes post	0.077 (0.06)	0.050 (0.016)

5. Secondary Outcome

Title	Peripheral Oxygen Saturation
Description	A finger pulse oximeter allowed for the measurement of peripheral oxygen saturation at baseline, 30-, 60- and 90-minutes post albuterol in cystic fibrosis and healthy subjects.
Time Frame	baseline, 30-, 60- and 90-minutes post albuterol

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy	Cystic Fibrosis
Arm/Group Description	Healthy control subjects	Patients diagnosed with cystic fibrosis
Measure Participants	16	16
Baseline	99 (1)	98 (1)
30 minutes post	100 (0)	98 (1)
60 minutes post	99 (1)	98 (1)
90 minutes post	99 (1)	99 (1)

Adverse Events

Time Frame	Within the study visit (~2 hours)
Arm/Group Title	Healthy		Cystic Fibrosis
Arm/Group Description	Healthy control subjects		Patients diagnosed with cystic fibrosis
All Cause Mortality
	Healthy		Cystic Fibrosis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Healthy		Cystic Fibrosis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Healthy		Cystic Fibrosis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (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.