C1-inhibitor in Allergic ASThma Patients (CAST)

T. van der Poll

Status and phase: Terminated; Phase 4

Conditions: Asthma

Treatments: Drug: C1-inhibitor; Other: Saline; Drug: Antibiotics

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03051698

2015_024

Details and patient eligibility

About

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

Full 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.

Enrollment: 37 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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37 participants in 3 patient groups, including a placebo group

C1-inhibitor

Experimental group

Description:

One gift of intravenous administration of C1-inhibitor (Cinryze, 100U/kg) during one hour

Treatment:

Drug: C1-inhibitor

Saline

Placebo Comparator group

Description:

One gift of intravenous administration of 0.9% NaCl during one hour.

Treatment:

Other: Saline

Antibiotics

Experimental group

Description:

broad spectrum antibiotics (vancomycin, ciprofloxacin, metronidazole) for 7 days (washout 36 hours before study day).

Treatment:

Drug: Antibiotics