Interactive Acute Smooth Muscle Effects of Salmeterol and Fluticasone in the Airway - Full Text View

Purpose

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	Intervention
Asthma	Drug: fluticasone Drug: placebo inhalation Drug: Salmeterol Drug: fluticasone/salmeterol

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator)
Official Title:	Interactive Acute Smooth Muscle Effects of Salmeterol and Fluticasone in the Airway

Resource links provided by NLM:

MedlinePlus related topics: Asthma Steroids

Drug Information available for: Fluticasone propionate Salmeterol Fluticasone Salmeterol xinafoate

U.S. FDA Resources

Further study details as provided by University of Miami:

Primary Outcome Measures:

airway blood flow (Qaw) [ Time Frame: immediately after inhalation of salmeterol ] [ Designated as safety issue: No ]
Qaw will be measured before and at 5, 15, 30, 60, 120, and 240 min after inhalation of salmeterol
Airway Blood Flow (Qaw) [ Time Frame: immediately after inhalation of fluticasone ] [ Designated as safety issue: No ]
Qaw will be measured before and at 5, 15, 30, 60, 120, and 240 min after inhalation of fluticasone
Airway Blood Flow (Qaw) [ Time Frame: immediately after inhalation of fluticasone/salmeterol ] [ Designated as safety issue: No ]
Qaw will be measured before and at 5, 15, 30, 60, 120, and 240 min after inhalation of fluticasone/salmeterol

Secondary Outcome Measures:

Spirometry [ Time Frame: immediately after inhalation of salmeterol ] [ Designated as safety issue: No ]
Spirometry will be measured before and at 5, 15, 30, 60, 120, and 240 min after inhalation of salmeterol
spirometry [ Time Frame: immediately after inhalation of fluticasone/salmeterol ] [ Designated as safety issue: No ]
Spirometry will be measured before and at 5, 15, 30, 60, 120, and 240 min after inhalation of fluticasone/salmeterol
Spirometry [ Time Frame: immediately after inhalation of fluticasone ] [ Designated as safety issue: No ]
Spirometry will be measured before and at 5, 15, 30, 60, 120, and 240 min after inhalation of fluticasone

Enrollment:	20
Study Start Date:	May 2007
Study Completion Date:	August 2010
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: fluticasone inhalation of 250 mcg of fluticasone	Drug: fluticasone 220- mcg once
Placebo Comparator: placebo inhalation of placebo diskus	Drug: placebo inhalation placebo inhalation once
Active Comparator: salmeterol inhalation of salmeterol 50 mcg once	Drug: Salmeterol 50 mcg salmeterol once Drug: Salmeterol 50 mcg once
Active Comparator: fluticasone/salmeterol inhalation of fluticasone 250mcg combined with salmeterol 50 mcg	Drug: fluticasone/salmeterol inhalation of 250 mcg of fluticasone combined with 50 mcg of salmeterol

Detailed Description:

Twenty lifetime nonsmokers with a physician diagnosis of asthma will be recruited for the study. Ten of them will be subjects who do not use inhaled glucocorticosteroids and/or regular long-acting beta-adrenergic agonists, and 10 will be subjects who have been using salmeterol/fluticasone (50/250 μg) regularly twice a day as a controller for at least 4 weeks. All subjects will be allowed to use short-acting beta-adrenergic agonists as rescue medication.

Inclusion criteria:

Males and females, 18 to 65 years of age.
FEV1 60-85% of predicted on the screening day.

Exclusion criteria:

Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women.
Cardiovascular disease and/or use of cardiovascular medications

2. 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

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males and females, 18 to 65 years of age.
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

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Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided by University of Miami

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mendes ES, Rebolledo P, Wanner A. Acute effects of salmeterol and fluticasone propionate alone and in combination on airway blood flow in patients with asthma. Chest. 2012 May;141(5):1184-9. Epub 2011 Oct 6.

Responsible Party:	Adam Wanner, MD, University of Miami
ClinicalTrials.gov Identifier:	NCT01231230 History of Changes
Other Study ID Numbers:	20060346
Study First Received:	October 25, 2010
Last Updated:	October 29, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Miami:

asthma, inhaled corticosteroids, long-acting bronchodilator, airway blood flow

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Salmeterol
Albuterol
Fluticasone
Fluticasone, salmeterol drug combination
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists

Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents
Reproductive Control Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on May 23, 2013