C1-inhibitor in Allergic ASThma Patients

Phase 4TerminatedNCT03051698

T. van der Poll37 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Asthma

Interventions

C1-inhibitorDRUG

100 Unit/kg IV, one gift prior to broncho provocation.

SalineOTHER

0.9% NaCl

AntibioticsDRUG

vancomycin, ciprofloxacin, metronidazole

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (1)

Academic Medical Center

Amsterdam, North Holland, Netherlands

Outcomes

Primary Outcomes

Influx of inflammatory cells in the lung

Most important cell types are the eosinophils and neutrophils in bronchoaveolar fluid

Time frame: 7 hours after bronchial instillation of house dust mite (HDM) and lipopolyssacharide(LPS)