C1-inhibitor in Allergic ASThma Patients (CAST)

June 23, 2020 updated by: T. van der Poll

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
37

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
        • Academic Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: C1-inhibitor
One gift of intravenous administration of C1-inhibitor (Cinryze, 100U/kg) during one hour
Drug: C1-inhibitor
100 Unit/kg IV, one gift prior to broncho provocation.
Other Names:
  • Cinryze
Placebo Comparator: Saline
One gift of intravenous administration of 0.9% NaCl during one hour.
Other: Saline
0.9% NaCl
Experimental: Antibiotics
broad spectrum antibiotics (vancomycin, ciprofloxacin, metronidazole) for 7 days (washout 36 hours before study day).
Drug: Antibiotics
vancomycin, ciprofloxacin, metronidazole
Other Names:
  • vancomycin, ciprofloxacin, metronidazole

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Influx of inflammatory cells in the lung
Time Frame: 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
7 hours after bronchial instillation of house dust mite (HDM) and lipopolyssacharide(LPS)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Interleukin-4 in pg/ml.
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
Interleukin-5 in pg/ml.
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
IL-13 in pg/ml.
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
IL-10 in pg/ml.
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
IFN-Y in pg/ml.
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
TNF-α in pg/ml.
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
CCL11 in pg/ml.
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
Interleukin-6 in pg/ml.
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
C4bc u/ml
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
C3bc u/ml
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
iC3b u/ml
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
C5a ng/ml
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
C5b-9 u/ml.
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
C3a in ng/ml
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
FXIIa activity in OD
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
FXIa in OD
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
FXIIa- C1-inhibitor complexes u/ml
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
kallikrein-C1-inhibitor complexes u/ml
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
high-molecular weight kininogen in AU
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS
thrombin-antithrombin complexes in ng/ml.
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
C1-inhibitor activity in bronchoalveolar lavage
Time Frame: 7 hours after bronchial instillation of HDM and LPS
7 hours after bronchial instillation of HDM and LPS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
T. van der Poll

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
ZonMw: The Netherlands Organisation for Health Research and Development
Prothya Biosolutions

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tom vd Poll, Prof, dr, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 16, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 23, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 23, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 7, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 14, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 24, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 23, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2015_024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Asthma

Clinical Trials on Saline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings