C1-inhibitor in Allergic ASThma Patients
- Conditions
- Asthma
- Interventions
- Other: SalineDrug: C1-inhibitorDrug: Antibiotics
- Registration Number
- NCT03051698
- Lead Sponsor
- T. van der Poll
- Brief Summary
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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 37
- 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 < 1,2.
- Written informed consent
- No current smoking for at least 1 year and less than 10 pack years of smoking history
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Saline Saline One gift of intravenous administration of 0.9% NaCl during one hour. C1-inhibitor C1-inhibitor One gift of intravenous administration of C1-inhibitor (Cinryze, 100U/kg) during one hour Antibiotics Antibiotics broad spectrum antibiotics (vancomycin, ciprofloxacin, metronidazole) for 7 days (washout 36 hours before study day).
- Primary Outcome Measures
Name Time Method Influx of inflammatory cells in the lung 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
- Secondary Outcome Measures
Name Time Method 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 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 activity in OD 7 hours after bronchial instillation of HDM and LPS FXIa in OD 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
Trial Locations
- Locations (1)
Academic Medical Center
🇳🇱Amsterdam, Noord-Holland, Netherlands