Acute Effect of Mometasone on Beta-adrenergic Airway and Airway Vascular Relaxation in Severe Asthma
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- 適用できない
連絡先と場所
研究場所
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Florida
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Miami、Florida、アメリカ、33136
- Human Research Laboratory- University of Miami School of Medicine
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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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研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：他の
- 割り当て：ランダム化
- 介入モデル：単一グループの割り当て
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：mometasone 400 mcg - 30 min
randomly assigned intervention
|
mometasone inhalation before albuterol.
他の名前：
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実験的：mometasone 400 mcg simultaneous
randomly assigned intervention
|
mometasone inhalation before albuterol.
他の名前：
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プラセボコンパレーター：placebo- 30 min
randomly assigned intervention
|
placebo inhalation before albuterol.
他の名前：
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プラセボコンパレーター：placebo simultaneous
randomly assigned intervention
|
placebo inhalation before albuterol.
他の名前：
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実験的：mometasone 400 mcg - 60 min
randomly assigned intervention
|
mometasone inhalation before albuterol.
他の名前：
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プラセボコンパレーター：placebo- 60 min
randomly assigned intervention
|
placebo inhalation before albuterol.
他の名前：
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実験的：mometasone 200 mcg - 30 min
randomly assigned intervention
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200ug mometasone before albuterol.
他の名前：
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実験的：mometasone 200 mcg - 60 min
randomly assigned intervention
|
200ug mometasone before albuterol.
他の名前：
|
|
実験的：mometasone 200 mcg simultaneous
randomly assigned intervention
|
200ug mometasone before albuterol.
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Albuterol-induced Change in FEV1
時間枠：15 minutes after albuterol inhalation
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FEV1 will be measured before and after inhalation of 180 mcg albuterol.
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15 minutes after albuterol inhalation
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Albuterol Induced Percent Change in Qaw
時間枠：change in Qaw 15 minutes after albuterol inhalation
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Qaw will be measured before and 15 min after albuterol inhalation
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change in Qaw 15 minutes after albuterol inhalation
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協力者と研究者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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