Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

C1-inhibitor in Allergic ASThma Patients (CAST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03051698
Recruitment Status : Terminated (Interim analysis showed no differences between groups)
First Posted : February 14, 2017
Last Update Posted : June 24, 2020
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Sanquin Plasma Products BV
Information provided by (Responsible Party):
T. van der Poll, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Tracking Information
First Submitted Date  ICMJE February 7, 2017
First Posted Date  ICMJE February 14, 2017
Last Update Posted Date June 24, 2020
Actual Study Start Date  ICMJE November 16, 2016
Actual Primary Completion Date October 23, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2017)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2017)
  • Interleukin-4 in pg/ml. [ Time Frame: 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 ]
  • IL-13 in pg/ml. [ Time Frame: 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 ]
  • IFN-Y in pg/ml. [ Time Frame: 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 ]
  • CCL11 in pg/ml. [ Time Frame: 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 ]
  • C4bc u/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  • C3bc u/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  • iC3b u/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  • C5a ng/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  • C5b-9 u/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  • C3a in ng/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  • FXIIa activity in OD [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  • FXIa in OD [ Time Frame: 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 ]
  • kallikrein-C1-inhibitor complexes u/ml [ Time Frame: 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 ]
  • thrombin-antithrombin complexes in ng/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 9, 2017)
C1-inhibitor activity in bronchoalveolar lavage [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE C1-inhibitor in Allergic ASThma Patients
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: C1-inhibitor
    100 Unit/kg IV, one gift prior to broncho provocation.
    Other Name: Cinryze
  • Other: Saline
    0.9% NaCl
  • Drug: Antibiotics
    vancomycin, ciprofloxacin, metronidazole
    Other Name: vancomycin, ciprofloxacin, metronidazole
Study Arms  ICMJE
  • Experimental: C1-inhibitor
    One gift of intravenous administration of C1-inhibitor (Cinryze, 100U/kg) during one hour
    Intervention: Drug: C1-inhibitor
  • Placebo Comparator: Saline
    One gift of intravenous administration of 0.9% NaCl during one hour.
    Intervention: Other: Saline
  • Experimental: Antibiotics
    broad spectrum antibiotics (vancomycin, ciprofloxacin, metronidazole) for 7 days (washout 36 hours before study day).
    Intervention: Drug: Antibiotics
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 23, 2020)
37
Original Estimated Enrollment  ICMJE
 (submitted: February 9, 2017)
60
Actual Study Completion Date  ICMJE October 23, 2019
Actual Primary Completion Date October 23, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03051698
Other Study ID Numbers  ICMJE 2015_024
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party T. van der Poll, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study Sponsor  ICMJE T. van der Poll
Collaborators  ICMJE
  • ZonMw: The Netherlands Organisation for Health Research and Development
  • Sanquin Plasma Products BV
Investigators  ICMJE
Principal Investigator: Tom vd Poll, Prof, dr, MD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
PRS Account Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP