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Acute Effect of Mometasone on Beta-adrenergic Airway and Airway Vascular Relaxation in Severe Asthma

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Adam Wanner, University of Miami
ClinicalTrials.gov Identifier:
NCT01210170
First received: September 27, 2010
Last updated: May 27, 2016
Last verified: May 2016
  Purpose

Glucocorticosteroids inhibit the disposal of organic cations by blocking organic cation transporters expressed by non-neuronal cells, thereby interfering with the inactivation of the organic cations by intracellular enzymes. Beta2-adrenergic agonists are organic cations, and the concentration of inhaled beta2-adrenergic agonists at beta2-adrenergic receptor sites on smooth muscle is likely to be increased by inhaled glucocorticosteroids (ICS) by the ICS' effect on the glucocorticosteroid-sensitive organic cation transporters. The investigators have shown in human airway vascular smooth muscle cells that the glucocorticosteroid action on organic cation uptake occurs within minutes, does not involve gene transcription or protein synthesis, is not mediated through classical steroid receptors, and is cell membrane-linked.

In the present proposal, the investigators wish to use different single doses of mometasone, a clinically effective ICS, administered with or at different times before albuterol inhalation in subjects with moderate persistent asthma who are obstructed at the time of study.

With this approach the investigators will test the hypothesis that a single inhalation of mometasone causes an acute, transient, dose-dependent potentiation of beta2-adrenergic bronchodilation.

If the hypothesis that a single dose of mometasone acutely potentiates beta2-adrenergic bronchodilation is correct, the results would have a significant impact on treatment strategies involving ICSs and beta2-adrenergic agonists in patients with asthma.


Condition Intervention
Asthma
Drug: placebo 30min
Drug: mometasone 400 mcg 30min
Drug: placebo comparator simultaneous
Drug: mometasone simultaneous

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Acute Effect of Mometasone Furoate DPI on Beta-adrenergic Airway and Airway Vascular Relaxation in Moderately Severe Asthma

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Albuterol-induced Change in FEV1 [ Time Frame: 15 minutes after albuterol inhalation ] [ Designated as safety issue: No ]
    FEV1 will be measured before and after inhalation of 180 mcg albuterol.


Secondary Outcome Measures:
  • Albuterol Induced Percent Change in Qaw [ Time Frame: change in Qaw 15 minutes after albuterol inhalation ] [ Designated as safety issue: No ]
    Qaw will be measured before and 15 min after albuterol inhalation


Enrollment: 22
Study Start Date: October 2010
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: mometasone 400 mcg - 30 min
randomly assigned intervention
Drug: mometasone 400 mcg 30min
mometasone inhalation 30 min before albuetrol
Other Name: Asmanex
Experimental: mometasone 400 mcg simultaneous
randomly assigned intervention
Drug: mometasone simultaneous
400ug mometasone simultaneously with albuterol
Placebo Comparator: placebo- 30 min
randomly assigned intervention
Drug: placebo 30min
placebo inhalation 30min before albuterol
Placebo Comparator: placebo simultaneous
randomly assigned intervention
Drug: placebo comparator simultaneous
placebo inhalation simultaneous with albuterol

Detailed Description:

Fifteen non-smokers (males and females between the ages of 18 and 65 years) with physician-diagnosed moderate persistent asthma will be recruited for the study. The subjects will be allowed to use inhaled controller (including ICS) and rescue medication. At study entry, all asthmatic subjects must be clinically stable, and have a forced pre-bronchodilator one-second expired volume (FEV1) of < 75% predicted.

Approval for the protocol will be requested from the University of Miami Institutional Review Board. All subjects will provide written informed consent.

Exclusion criteria:

  • Cardiovascular disease and use of cardiovascular medications
  • Pregnancy
  • Use of oral controller medication for asthma (methylxanthines, systemic glucocorticosteroids, leukotriene modifiers)
  • An acute respiratory infection within 4 weeks before enrollment.

Each subject will make 8 visits to the research laboratory.

Procedures:

Visit 1 (screening visit): On this visit, after having signed the consent form, the subjects will perform spirometry before and 15 min after inhaling 180 µg albuterol from a HFA-MDI using a spacer.

Visit 2-8:Subjects that qualify for the study will be asked to return for 7 more visits for the following treatment protocols:

  • Inhalation of 400 µg mometasone 30 min before inhalation of 180 µg albuterol
  • Inhalation of mometasone placebo 30 min before inhalation of 180 µg albuterol
  • Simultaneous inhalation of 400 µg mometasone and 180 µg albuterol
  • Simultaneous inhalation of mometasone placebo and 180 µg albuterol

Systemic blood pressure, pulse, O2 saturation, spirometry and airway blood flow ( Qaw) will be measured before mometasone or placebo inhalation, and before and 15 min after albuterol inhalation except on the day when mometasone and albuterol are co-administered; on that day the measurements will be made before and 15 min after the mometasone/albuterol co-administration.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:Fifteen non-smokers (males and females between the ages of 18 and 65 years) with physician-diagnosed moderate persistent asthma and FEV1 < 75% of predicted.

Exclusion Criteria:Cardiovascular disease and use of cardiovascular medications, pregnancy, use of oral controller medication for asthma (methylxanthines, systemic glucocorticosteroids, leukotriene modifiers), an acute respiratory infection within 4 weeks before enrollment

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01210170

Locations
United States, Florida
Human Research Laboratory- University of Miami School of Medicine
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Adam Wanner University of Miami
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Adam Wanner, Professor of Medicine, University of Miami
ClinicalTrials.gov Identifier: NCT01210170     History of Changes
Other Study ID Numbers: 20071188  P05299 
Study First Received: September 27, 2010
Results First Received: September 5, 2014
Last Updated: May 27, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
asthma,
inhaled corticosteroids,
airway blood flow,
mometasone,
albuterol
spirometry

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Adrenergic Agents
Mometasone Furoate
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Dermatologic Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on September 23, 2016