Effect of Intravenous Administration of C1-inhibitor on Inflammation and Coagulation After Bronchial Instillation of House Dust Mite Allergen and Lipopolysaccharide in Allergic Asthma Patients
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Influx of inflammatory cells in the lung
研究概览
简要总结
The purpose of this proof-of-concept study is to determine the effect of Intestinal Microbiota Depletion or Intravenous Administration of C1-inhibitor on Inflammation and Coagulation after Bronchial Instillation of House Dust Mite Allergen and Lipopolysaccharide in Allergic Asthma Patients
详细描述
Intravenous administration of C1-inhibitor (n=20) or vehicle (n=20). One group of patients (n=20) will receive broad spectrum antibiotics (vancomycin, ciprofloxacin, metronidazole) for 7 days (washout 36 hours before study day). This group will receive the same vehicle as the control group 2 hours prior to challenge. HDM will be administered together with the environmental pollutant LPS in a lung subsegment via a bronchoscope (mimicking environmental exposure to HDM); a contralateral lung subsegment will be administered with saline (control side). After 7 hours, bronchoalveolar lavage (BAL) fluid will be harvested by a second bronchoscopy. Blood samples will be collected before administration of C1-inhibitor or vehicle, and before both bronchoscopies. Faeces will be collected prior to antibiotic administration as well as prior to HDM+LPS challenge.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Intermittent to mild asthma according to the Global Initiative for Asthma (GINA) criteria
- •Allergy for HDM documented by a positive RAST and a positive skin prick test.
- •No clinically significant findings during physical examination and hematological and biochemical screening
- •At spirometry FEV1 more than 70% of predicted value
- •A PC20 between 0.3 - 9.6 mg/ml (corresponding with increased airway hyperreactivity)
- •Able to communicate well with the investigator and to comply with the requirements of the study
- •Stable asthma without the use of asthma medication 2 weeks prior to the study day. As documented by the Juniper's Asthma control questionnaire (ACQ) score < 1,
- •Written informed consent
- •No current smoking for at least 1 year and less than 10 pack years of smoking history
排除标准
- •Relevant comorbidity, pregnancy and/or recent surgical procedures.
- •A history of smoking within the last 12 months, or regular consumption of greater than three units of alcohol per day
- •Exacerbation and/ or the use of asthma medication within 2 weeks before start
- •Administration of any investigational drug within 30 days of study initiation
- •Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation]
- •History of venous or arterial thromboembolic disease
- •History of enhanced bleeding tendency or abnormal clotting test results.
- •History of serious drug-related reactions, including hypersensitivity
- •Inability to maintain stable without the use of asthma medication 2 weeks before start of the study
研究组 & 干预措施
C1-inhibitor
One gift of intravenous administration of C1-inhibitor (Cinryze, 100U/kg) during one hour
干预措施: C1-inhibitor (Drug)
Saline
One gift of intravenous administration of 0.9% NaCl during one hour.
干预措施: Saline (Other)
Antibiotics
broad spectrum antibiotics (vancomycin, ciprofloxacin, metronidazole) for 7 days (washout 36 hours before study day).
干预措施: Antibiotics (Drug)
结局指标
主要结局
Influx of inflammatory cells in the lung
时间窗: 7 hours after bronchial instillation of house dust mite (HDM) and lipopolyssacharide(LPS)
Most important cell types are the eosinophils and neutrophils in bronchoaveolar fluid
次要结局
- FXIa in OD(7 hours after bronchial instillation of HDM and LPS)
- high-molecular weight kininogen in AU(7 hours after bronchial instillation of HDM and LPS)
- thrombin-antithrombin complexes in ng/ml.(7 hours after bronchial instillation of HDM and LPS)
- FXIIa activity in OD(7 hours after bronchial instillation of HDM and LPS)
- Interleukin-4 in pg/ml.(7 hours after bronchial instillation of HDM and LPS)
- Interleukin-5 in pg/ml.(7 hours after bronchial instillation of HDM and LPS)
- IL-13 in pg/ml.(7 hours after bronchial instillation of HDM and LPS)
- IL-10 in pg/ml.(7 hours after bronchial instillation of HDM and LPS)
- IFN-Y in pg/ml.(7 hours after bronchial instillation of HDM and LPS)
- TNF-α in pg/ml.(7 hours after bronchial instillation of HDM and LPS)
- CCL11 in pg/ml.(7 hours after bronchial instillation of HDM and LPS)
- Interleukin-6 in pg/ml.(7 hours after bronchial instillation of HDM and LPS)
- C4bc u/ml(7 hours after bronchial instillation of HDM and LPS)
- C3bc u/ml(7 hours after bronchial instillation of HDM and LPS)
- iC3b u/ml(7 hours after bronchial instillation of HDM and LPS)
- C5a ng/ml(7 hours after bronchial instillation of HDM and LPS)
- C5b-9 u/ml.(7 hours after bronchial instillation of HDM and LPS)
- C3a in ng/ml(7 hours after bronchial instillation of HDM and LPS)
- FXIIa- C1-inhibitor complexes u/ml(7 hours after bronchial instillation of HDM and LPS)
- kallikrein-C1-inhibitor complexes u/ml(7 hours after bronchial instillation of HDM and LPS)
研究者
T. van der Poll
Prof. dr.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)