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

Healthy Clinical Trial

Official title:

Modifying Genes in Cystic Fibrosis: The Beta-2 Adrenergic Receptors and Epithelial Na+ Channels

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01880723
• Other study ID #: 08-1123-01
• Secondary ID: 1R01HL108962-01
• Status: Completed
• Phase: N/A
• Start date: May 2009
• Est. completion date: January 2013

Study information

• Verified date: November 2023
• Source: University of Arizona
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: January 2013
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Healthy

Intervention

Drug:
• Albuterol
2.5 mg diluted in 3mL normal saline nebulized using a Power Neb2 nebulizer
• Placebo saline
nebulized 3mL normal saline) using a Power Neb2 nebulizer

Locations

Country	Name	City	State
United States	Department of Pharmacy Practice and Science, University of Arizona, Tucson, Arizona	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
University of Arizona	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Baker SE, Wheatley CM, Cassuto NA, Foxx-Lupo WT, Sprissler R, Snyder EM. Genetic variation of alphaENaC influences lung diffusion during exercise in humans. Respir Physiol Neurobiol. 2011 Dec 15;179(2-3):212-8. doi: 10.1016/j.resp.2011.08.007. Epub 2011 A — View Citation

Foxx-Lupo WT, Wheatley CM, Baker SE, Cassuto NA, Delamere NA, Snyder EM. Genetic variation of the alpha subunit of the epithelial Na+ channel influences exhaled Na+ in healthy humans. Respir Physiol Neurobiol. 2011 Dec 15;179(2-3):205-11. doi: 10.1016/j.r — View Citation

Snyder EM, Wong EC, Foxx-Lupo WT, Wheatley CM, Cassuto NA, Patanwala AE. Effects of an inhaled beta2-agonist on cardiovascular function and sympathetic activity in healthy subjects. Pharmacotherapy. 2011 Aug;31(8):748-56. doi: 10.1592/phco.31.8.748. — View Citation

Traylor BR, Wheatley CM, Skrentny TT Jr, Foxx-Lupo WT, Phan H, Patanwala AE, Morgan WJ, Daines CL, Sprissler R, Snyder EM. Influence of genetic variation of the beta2-adrenergic receptor on lung diffusion in patients with cystic fibrosis. Pulm Pharmacol T — View Citation

Wheatley CM, Foxx-Lupo WT, Cassuto NA, Wong EC, Daines CL, Morgan WJ, Snyder EM. Impaired lung diffusing capacity for nitric oxide and alveolar-capillary membrane conductance results in oxygen desaturation during exercise in patients with cystic fibrosis. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exhaled Sodium (mmol/L)	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.	up to 90-minutes post albuterol
Primary	Net Exhaled Chloride	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])	baseline to 90 minutes post albuterol administration
Secondary	Diffusion Capacity of the Lungs for Carbon Monoxide	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.	baseline, 30-, 60- and 90-minutes post albuterol administration
Secondary	Diffusion Capacity of the Lungs for Nitric Oxide	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.	baseline, 30-, 60- and 90-minutes post albuterol administration
Secondary	Peripheral Oxygen Saturation	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.	baseline, 30-, 60- and 90-minutes post albuterol