- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00180661
Inflammation and Corticosteroid Responsiveness in Severe Asthma (SARP)
Descripción general del estudio
Estado
Condiciones
Descripción detallada
Study Design Patients referred to the Royal Brompton Hospital with severe asthma will be entered into a protocol that will determine whether they have asthma, and if so, the severity and clinical features of their asthma. Patients will also undergo investigations relating to asthma as detailed below. We will use an agreed Severe Asthma Research protocol (SARP) screening system to diagnose asthma (history, bronchodilator response and presence of bronchial hyperresponsiveness) (Screening questionnaire in SARP Handbook). Usually, the protocol will be carried out while the patient is admitted over 3-night admission.
Patients will undergo fiberoptic bronchoscopy. We will obtain cells by bronchoalveolar lavage and bronchial biopsies of the airway mucosa. These cells and biopsies will be studied in vitro as to the expression of corticosteroid receptor nuclear translocation, expression of cytokines, and the degree of histone acetylation/deacetylation status. These findings will be compared to those cells and biopsies obtained from mild and moderately severe asthma.
In a subgroup of patients with severe asthma, patients will be treated with oral prednisolone 40 mg/day or increase in maintenance dose of prednisolone by 40 mg/day. Fiberoptic bronchoscopy will then be repeated.
Details of the interventions proposed Some of the interventions listed below are in routine clinical use for investigation of severe asthma. For example, the computed tomogram is only ordered on clinical grounds. A fiberoptic bronchoscopy will be performed.
- Demographic history and history of their symptoms of asthma and treatments using a comprehensive questionnaire
- Quality of life questionnaire (AQLQ)
- Skin prick tests to 16 common allergens
- Measuring lung function tests
- Bronchial responsiveness to methacholine
- Bronchial reversibility test to inhaled salbutamol
- Keeping a diary card of symptoms, treatments and peak flows for 2 weeks
- Observance of compliance to treatments
- Provision of sample of sputum, spontaneous or induced
- Measuring exhaled nitric oxide; collecting of exhaled breath condensates
- Fiberoptic bronchoscopy to obtain bronchoalveolar lavage cells, bronchial brushings and bronchial biopsies
- Obtaining sample of blood for DNA extraction for genetic analysis
- Obtaining blood for blood mononuclear cells for in vitro analysis of the effects of corticosteroids In patients with mild-to-moderate asthma, test 8 will not be performed. The details of these interventions are enclosed in the SARP Handbook.
Sources and Recruitment of Subjects:
Patients will be recruited from all patients referred to the Royal Brompton Hospital with a referral diagnosis of severe or difficult asthma for further management. The Royal Brompton Hospital is recognized nationally as a center for referral of such patients.
7Inclusion criteria The final diagnosis of severe asthma will be made according to the screening steps we have set up. The definition will require the presence of one or both major criteria (treatment with continuous or near continuous oral corticosteroids and/or requirement for treatment with high dose inhaled steroids) and two minor criteria.
Patients who do not fit the criteria of severe asthma will not be entered into the study.
Age 18-60; both sexes.
For the investigation of fiberoptic bronchoscopy, other additional inclusion criteria will be imposed:
- Post-bronchodilator FEV1 greater than 40% on the day of the bronchoscopy
- No evidence of an exacerbation of asthma within the past 4 weeks.
- Ability to cooperate with procedures
- Ability to give consent
- The bronchoscopist has determined the subject is clinically appropriate for bronchoscopy
Patients will be excluded for fiberoptic bronchoscopy if:
- FEV1 is less than 35% predicted before or less than 40% predicted after bronchodilator administration
- Asthma is clinically unstable
- Communication channels is not established for follow-up contacts
- Clinically significant, unstable co-morbidities are present
Exclusion criteria Current smokers, and ex-smokers with greater than 10 pack years history of smoking.
Pregnancy or unreliable contraceptive measures in child-bearing woman.
Volunteer subjects We will need comparative asthmatic subjects with mild to moderately severe asthma. The groups will be defined as follows, according to their need for treatments (as established in the Asthma Management GINA or BTS guidelines): (i) Mild: intermittent symptoms and need for reliever bronchodilator less than once a day; (ii) moderate asthma: well-controlled asthma with minimal symptoms while on inhaled corticosteroid therapy not exceeding 2,000 microgram beclomethasone equivalent .
These patients will be recruited from the Asthma clinics attending the Royal Brompton Hospital, and also the milder patients will be recruited by advertisement within the Hospital, or from local general practices.
Current involvement in research The patients entered into this study will not be involved in any other research project, and must have Completed any other project within a month of entry into the current study. From previous experience, we aim to recruit 12 patients with severe asthma per year; in total, 50 patients with severe asthma over a 4 year period. Concomitantly, we will recruit 40 mild-to-moderately severe asthma patients. Pharmacology and Dispensing (i) substance: Prednisolone tablets (ii) route of administration: Oral (iii) frequency : once a day (iv) dosage: 30 mg/day (or addition of 30 mg on top of maintainence dose) (v) stage of CSM evaluation: n/a.
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
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London, Reino Unido, SW3 6HP
- Royal Brompton Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
The final diagnosis of severe asthma will be made according to the screening steps we have set up. The definition will require the presence of one or both major criteria (treatment with continuous or near continuous oral corticosteroids and/or requirement for treatment with high dose inhaled steroids) and two minor criteria.
Patients who do not fit the criteria of severe asthma will not be entered into the study.
Age 18-60; both sexes.
For the investigation of fiberoptic bronchoscopy, other additional inclusion criteria will be imposed:
- Post-bronchodilator FEV1 greater than 40% on the day of the bronchoscopy
- No evidence of an exacerbation of asthma within the past 4 weeks.
- Ability to cooperate with procedures
- Ability to give consent
- Current smokers, and ex-smokers with greater than 10 pack years history of smoking.
Exclusion criteria
Pregnancy or unreliable contraceptive measures in child-bearing woman. he bronchoscopist has determined the subject is clinically appropriate for bronchoscopy
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Exclusion Criteria:
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Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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Severe Asthma
Patients under Steps 4/5 of Asthma Treatment - SIGN/BTS Guidelines
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Moderate Asthma
Asthma patients on steps 2/3 of Asthma treatment according to SIGN/BTS Guidelines
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Mild Asthma
Asthma patients on steps 1 of asthma treatment (steroid naive).
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Lung Function FEV1
Periodo de tiempo: 1 day
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FEV1, or forced expiratory volume, is a measurement taken from a pulmonary function test.
It calculates the amount of air that a person can force out of their lungs in 1 second.
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1 day
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Suppression of Monocyte Activation and Alveolar Macrophage Activation by Dexamethasone Ex-vivo
Periodo de tiempo: 1 day
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IL8 - Interleukin-8 (IL-8) is a cytokine produced by many normal cells including monocytes, neutrophils, fibroblasts, and endothelial cells
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1 day
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Effect of Corticosteroids on Release of Cytokines From Macrophages
Periodo de tiempo: Once
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Once
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
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Exhaled NO
Periodo de tiempo: 1 day
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1 day
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Biopsy Eosinophils
Periodo de tiempo: Once
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Once
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Sputum Eosinophils
Periodo de tiempo: Once
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Once
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Publicaciones y enlaces útiles
Publicaciones Generales
- Chung KF, Godard P, Adelroth E, Ayres J, Barnes N, Barnes P, Bel E, Burney P, Chanez P, Connett G, Corrigan C, de Blic J, Fabbri L, Holgate ST, Ind P, Joos G, Kerstjens H, Leuenberger P, Lofdahl CG, McKenzie S, Magnussen H, Postma D, Saetta M, Salmeron S, Sterk P. Difficult/therapy-resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies. ERS Task Force on Difficult/Therapy-Resistant Asthma. European Respiratory Society. Eur Respir J. 1999 May;13(5):1198-208. doi: 10.1034/j.1399-3003.1999.13e43.x. No abstract available.
- Bhavsar P, Hew M, Khorasani N, Torrego A, Barnes PJ, Adcock I, Chung KF. Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma. Thorax. 2008 Sep;63(9):784-90. doi: 10.1136/thx.2007.090027. Epub 2008 May 20.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- HL-69155
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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