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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Não aplicável
Contactos e Locais
Locais de estudo
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Florida
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Miami, Florida, Estados Unidos, 33136
- Human Research Laboratory- University of Miami School of Medicine
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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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Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Outro
- Alocação: Randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: mometasone 400 mcg - 30 min
randomly assigned intervention
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mometasone inhalation before albuterol.
Outros nomes:
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Experimental: mometasone 400 mcg simultaneous
randomly assigned intervention
|
mometasone inhalation before albuterol.
Outros nomes:
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Comparador de Placebo: placebo- 30 min
randomly assigned intervention
|
placebo inhalation before albuterol.
Outros nomes:
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Comparador de Placebo: placebo simultaneous
randomly assigned intervention
|
placebo inhalation before albuterol.
Outros nomes:
|
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Experimental: mometasone 400 mcg - 60 min
randomly assigned intervention
|
mometasone inhalation before albuterol.
Outros nomes:
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Comparador de Placebo: placebo- 60 min
randomly assigned intervention
|
placebo inhalation before albuterol.
Outros nomes:
|
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Experimental: mometasone 200 mcg - 30 min
randomly assigned intervention
|
200ug mometasone before albuterol.
Outros nomes:
|
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Experimental: mometasone 200 mcg - 60 min
randomly assigned intervention
|
200ug mometasone before albuterol.
Outros nomes:
|
|
Experimental: mometasone 200 mcg simultaneous
randomly assigned intervention
|
200ug mometasone before albuterol.
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Albuterol-induced Change in FEV1
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Albuterol Induced Percent Change in Qaw
Prazo: 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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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Adam Wanner, University of Miami
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 20071188
- P05299 (Outro identificador: Sponsor)
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