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C1-inhibitor in Allergic ASThma Patients (CAST)

Primary Purpose

Asthma

Status

Terminated

Phase

Phase 4

Locations

Netherlands

Study Type

Interventional

Intervention

C1-inhibitor

Saline

Antibiotics

About this trial

This is an interventional treatment trial for Asthma focused on measuring C1-inhibitor, house dust mite, complement system

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept 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

Sites / Locations

Academic Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

C1-inhibitor

Saline

Antibiotics

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Influx of inflammatory cells in the lung

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

Secondary Outcome Measures

Interleukin-4 in pg/ml.

Interleukin-5 in pg/ml.

IL-13 in pg/ml.

IL-10 in pg/ml.

IFN-Y in pg/ml.

TNF-α in pg/ml.

CCL11 in pg/ml.

Interleukin-6 in pg/ml.

C4bc u/ml

C3bc u/ml

iC3b u/ml

C5a ng/ml

C5b-9 u/ml.

C3a in ng/ml

FXIIa activity in OD

FXIa in OD

FXIIa- C1-inhibitor complexes u/ml

kallikrein-C1-inhibitor complexes u/ml

high-molecular weight kininogen in AU

thrombin-antithrombin complexes in ng/ml.

Full Information

NCT ID

NCT03051698

First Posted

February 7, 2017

Last Updated

June 23, 2020

Sponsor

T. van der Poll

Collaborators

ZonMw: The Netherlands Organisation for Health Research and Development, Prothya Biosolutions

1. Study Identification

Unique Protocol Identification Number

NCT03051698

Brief Title

C1-inhibitor in Allergic ASThma Patients

Acronym

CAST

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Terminated

Why Stopped

Interim analysis showed no differences between groups

Study Start Date

November 16, 2016 (Actual)

Primary Completion Date

October 23, 2019 (Actual)

Study Completion Date

October 23, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

T. van der Poll

Collaborators

ZonMw: The Netherlands Organisation for Health Research and Development, Prothya Biosolutions

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Asthma

Keywords

C1-inhibitor, house dust mite, complement system

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

C1-inhibitor

Arm Type

Experimental

Arm Description

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

Arm Title

Saline

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Antibiotics

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

C1-inhibitor

Other Intervention Name(s)

Cinryze

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Saline

Intervention Description

0.9% NaCl

Intervention Type

Drug

Intervention Name(s)

Antibiotics

Other Intervention Name(s)

vancomycin, ciprofloxacin, metronidazole

Intervention Description

vancomycin, ciprofloxacin, metronidazole

Primary Outcome Measure Information:

Title

Influx of inflammatory cells in the lung

Description

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)

Secondary Outcome Measure Information:

Title

Interleukin-4 in pg/ml.

Time Frame