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

NCT01210170 | Completed Results

• 2 other identifiers: 20071188P05299
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma

Keywords

asthma,; inhaled corticosteroids,; airway blood flow,; mometasone,; albuterol; spirometry

Outcome Measures

Primary Outcomes (1)

• Albuterol-induced Change in FEV1

  FEV1 will be measured before and after inhalation of 180 mcg albuterol.

  15 minutes after albuterol inhalation

Secondary Outcomes (1)

• Albuterol Induced Percent Change in Qaw

  change in Qaw 15 minutes after albuterol inhalation

Study Arms (9)

mometasone 400 mcg - 30 min

EXPERIMENTAL

randomly assigned intervention

Drug: mometasone 400 mcg

mometasone 400 mcg simultaneous

EXPERIMENTAL

randomly assigned intervention

Drug: mometasone 400 mcg

placebo- 30 min

PLACEBO COMPARATOR

randomly assigned intervention

Drug: placebo

placebo simultaneous

PLACEBO COMPARATOR

randomly assigned intervention

Drug: placebo

mometasone 400 mcg - 60 min

EXPERIMENTAL

randomly assigned intervention

Drug: mometasone 400 mcg

placebo- 60 min

PLACEBO COMPARATOR

randomly assigned intervention

Drug: placebo

mometasone 200 mcg - 30 min

EXPERIMENTAL

randomly assigned intervention

Drug: mometasone 200 mcg

mometasone 200 mcg - 60 min

EXPERIMENTAL

randomly assigned intervention

Drug: mometasone 200 mcg

mometasone 200 mcg simultaneous

EXPERIMENTAL

randomly assigned intervention

Drug: mometasone 200 mcg

Interventions

placebo DRUG

placebo inhalation before albuterol.

Also known as: Asmanex placebo

placebo simultaneous; placebo- 30 min; placebo- 60 min

mometasone 400 mcg DRUG

mometasone inhalation before albuterol.

Also known as: Asmanex

mometasone 400 mcg - 30 min; mometasone 400 mcg - 60 min; mometasone 400 mcg simultaneous

mometasone 200 mcg DRUG

200ug mometasone before albuterol.

Also known as: Asmanex

mometasone 200 mcg - 30 min; mometasone 200 mcg - 60 min; mometasone 200 mcg simultaneous

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• University of Miami: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Human Research Laboratory- University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

Related Publications (1)

• Mendes ES, Cadet L, Arana J, Wanner A. Acute effect of an inhaled glucocorticosteroid on albuterol-induced bronchodilation in patients with moderately severe asthma. Chest. 2015 Apr;147(4):1037-1042. doi: 10.1378/chest.14-1742.

  PMID: 25611803 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Mometasone Furoate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Adam Wanner, MD
• Organization: University of Miami

awanner@med.miami.edu

(305) 243-2568

Study Officials

• Adam Wanner

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 27, 2010
• First Posted: September 28, 2010
• Study Start: October 1, 2010
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: November 21, 2017
• Results First Posted: November 19, 2014

Record last verified: 2017-10

Locations

US (1)