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

October 20, 2017 updated by: Adam Wanner, University of Miami

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • Human Research Laboratory- University of Miami School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: mometasone 400 mcg - 30 min
randomly assigned intervention
Drug: mometasone 400 mcg
mometasone inhalation before albuterol.
Other Names:
  • Asmanex
Experimental: mometasone 400 mcg simultaneous
randomly assigned intervention
Drug: mometasone 400 mcg
mometasone inhalation before albuterol.
Other Names:
  • Asmanex
Placebo Comparator: placebo- 30 min
randomly assigned intervention
Drug: placebo
placebo inhalation before albuterol.
Other Names:
  • Asmanex placebo
Placebo Comparator: placebo simultaneous
randomly assigned intervention
Drug: placebo
placebo inhalation before albuterol.
Other Names:
  • Asmanex placebo
Experimental: mometasone 400 mcg - 60 min
randomly assigned intervention
Drug: mometasone 400 mcg
mometasone inhalation before albuterol.
Other Names:
  • Asmanex
Placebo Comparator: placebo- 60 min
randomly assigned intervention
Drug: placebo
placebo inhalation before albuterol.
Other Names:
  • Asmanex placebo
Experimental: mometasone 200 mcg - 30 min
randomly assigned intervention
Drug: mometasone 200 mcg
200ug mometasone before albuterol.
Other Names:
  • Asmanex
Experimental: mometasone 200 mcg - 60 min
randomly assigned intervention
Drug: mometasone 200 mcg
200ug mometasone before albuterol.
Other Names:
  • Asmanex
Experimental: mometasone 200 mcg simultaneous
randomly assigned intervention
Drug: mometasone 200 mcg
200ug mometasone before albuterol.
Other Names:
  • Asmanex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Albuterol-induced Change in FEV1
Time Frame: 15 minutes after albuterol inhalation
FEV1 will be measured before and after inhalation of 180 mcg albuterol.
15 minutes after albuterol inhalation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Albuterol Induced Percent Change in Qaw
Time Frame: change in Qaw 15 minutes after albuterol inhalation
Qaw will be measured before and 15 min after albuterol inhalation
change in Qaw 15 minutes after albuterol inhalation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Miami

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Adam Wanner, University of Miami

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

February 1, 2013

Study Registration Dates

First Submitted

September 27, 2010

First Submitted That Met QC Criteria

September 27, 2010

First Posted (Estimate)

September 28, 2010

Study Record Updates

Last Update Posted (Actual)

November 21, 2017

Last Update Submitted That Met QC Criteria

October 20, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20071188
  • P05299 (Other Identifier: Sponsor)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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