Interactive Acute Smooth Muscle Effects of Salmeterol and Fluticasone in the Airway

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT01231230
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 14
• Arms: 4
• Duration (Months): 39

Study Details

Study Description

Brief Summary

The addition of an inhaled long-acting beta-adrenergic agonist to an inhaled glucocorticosteroid improves disease control in persistent asthma. This observation has supported the use of long-acting beta-adrenergic agonist/glucocorticosteroid combination preparations for the management of asthma. Currently, salmeterol/fluticasone and formoterol/budesonide are available for clinical use. The long-term beneficial clinical effects of the two drug classes seem to be synergistic, and several mechanisms of glucocorticoid-beta-adrenergic agonist interactions involving gene transcription have been invoked to explain this phenomenon.This study, wish to address the question whether glucocorticoids can acutely potentiate the bronchodilator response to a long-acting beta-adrenergic agonist.We expect that in patients with asthma, the short-term bronchodilator effect of salmeterol is enhanced by the addition of fluticasone, which by itself has no short-term bronchodilator effect. To test this premise, we will assess the respective short-term effects of salmeterol (50 µg), fluticasone (250 µg), salmeterol/fluticasone (50/250 µg), and placebo/placebo on spirometric parameters. Airway Blood flow will also be measured to ensure that vasoconstriction does not occur.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: fluticasone; Drug: placebo inhalation; Drug: Salmeterol; Drug: fluticasone/salmeterol	N/A

Detailed Description

Fourteen lifetime nonsmokers with a physician diagnosis of asthma will be recruited for the study. All subjects will be allowed to use short-acting beta-adrenergic agonists as rescue medication.

Inclusion criteria:

1. Males and females, 18 to 65 years of age.

2. FEV1 60-85% of predicted on the screening day.

Exclusion criteria:

1. Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women.

2. Cardiovascular disease and/or use of cardiovascular medications

3. Subjects with known beta-adrenergic agonist or glucocorticosteroid intolerance 4. Acute respiratory infection within four weeks prior to the study 5. Use, within two weeks prior to the study, of any anti-asthma medication not mentioned above

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Official Title: Interactive Acute Smooth Muscle Effects of Salmeterol and Fluticasone in the Airway
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: fluticasone/salmeterol participants were treated fluticasone/salmeterol,	Drug: fluticasone/salmeterol; inhalation of 250 mcg of fluticasone combined with 50 mcg of salmeterol; Other Names: advair
Experimental: salmeterol participants were treated with salmeterol	Drug: Salmeterol; 50 mcg salmeterol once; Other Names: serevent
Experimental: fluticasone participants were treated with fluticasone	Drug: fluticasone; 220- mcg once; Other Names: flovent
Placebo Comparator: placebo inhalation participants were treated with placebo	Drug: placebo inhalation; placebo inhalation once; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. Maximum Change From Baseline in Airway Blood Flow (Qaw) [maximum change in Qaw within 240 minutes post drug inhalation]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males and females, 18 to 65 years of age.

2. FEV1 60-85% of predicted on the screening day. -

Exclusion Criteria:

1. Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women. 2. Cardiovascular disease and/or use of cardiovascular medications 3. Subjects with known beta-adrenergic agonist or glucocorticosteroid intolerance 4. Acute respiratory infection within four weeks prior to the study 5. Use, within two weeks prior to the study, of any anti-asthma medication not mentioned above

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Miami
• GlaxoSmithKline

Investigators

• Principal Investigator: Adam Wanner, MD, University of Miami

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Adam Wanner, Professor of Medicine, University of Miami
• ClinicalTrials.gov Identifier: NCT01231230
• Other Study ID Numbers: 20060346
• First Posted: Nov 1, 2010
• Last Update Posted: Jun 30, 2016
• Last Verified: May 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Adam Wanner, Professor of Medicine, University of Miami: asthma, corticosteroids, bronchodilator, airway blood flow
• Additional relevant MeSH terms: Asthma; Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from our Asthma Database. Subjects with asthma who are in our database have previously agreed to serve as potential subjects in future studies. These subjects have signed an informed consent (approved by UM IRB) to be included in this database.

Arm/Group Title	All Study Groups
Arm/Group Description	inhalation of 250 mcg of fluticasone fluticasone: 220- mcg once
Period Title: Overall Study
STARTED	14
Fluticasone	14
Salmeterol	14
Fluticasone/Salmeterol	14
Placebo	14
COMPLETED	14
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	participant received in random order one of the four treatments ( fluticasone, salmeterol, fluticasone+salmeterol or placebo)
Overall Participants	14
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	9 64.3%
Male	5 35.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 21.4%
White	11 78.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%
Airway blood flow (Qaw) (µl.min-1.ml-1) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [µl.min-1.ml-1]	54.8 (2.6)

Outcome Measures

1. Primary Outcome

Title	Maximum Change From Baseline in Airway Blood Flow (Qaw)
Time Frame	maximum change in Qaw within 240 minutes post drug inhalation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluticasone	Placebo	Salmeterol	Fluticasone/Salmeterol
Arm/Group Description	inhalation of 250 mcg of fluticasone fluticasone: 220- mcg once	inhalation of placebo diskus placebo inhalation: placebo inhalation once	inhalation of salmeterol 50 mcg once Salmeterol: 50 mcg salmeterol once Salmeterol: 50 mcg once	inhalation of fluticasone 250mcg combined with salmeterol 50 mcg fluticasone/salmeterol: inhalation of 250 mcg of fluticasone combined with 50 mcg of salmeterol
Measure Participants	14	14	14	14
Mean (Standard Error) [change from baseline ( µl/min/ml)]	-11.0 (2.9)	14.1 (1.9)	23.9 (3.6)	25.5 (4.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluticasone/Salmeterol
	Comments	mean difference from baseline relative to placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Salmeterol
	Comments	mean difference from baseline relative to placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fluticasone, Placebo
	Comments	mean difference from baseline relative to placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANOVA
	Comments

Adverse Events

Arm/Group Title	Fluticasone		Placebo		Salmeterol		Fluticasone/Salmeterol
Arm/Group Description	inhalation of 250 mcg of fluticasone fluticasone: 220- mcg once		inhalation of placebo diskus placebo inhalation: placebo inhalation once		inhalation of salmeterol 50 mcg once Salmeterol: 50 mcg salmeterol once Salmeterol: 50 mcg once		inhalation of fluticasone 250mcg combined with salmeterol 50 mcg fluticasone/salmeterol: inhalation of 250 mcg of fluticasone combined with 50 mcg of salmeterol
All Cause Mortality
	Fluticasone		Placebo		Salmeterol		Fluticasone/Salmeterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Fluticasone		Placebo		Salmeterol		Fluticasone/Salmeterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)		0/14 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Fluticasone		Placebo		Salmeterol		Fluticasone/Salmeterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)		0/14 (0%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.