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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)

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

Condition or disease Intervention/treatment Phase
Asthma Drug: C1-inhibitor Other: Saline Drug: Antibiotics Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 16, 2016
Actual Primary Completion Date : October 23, 2019
Actual Study Completion Date : October 23, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
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 Name: 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 Name: vancomycin, ciprofloxacin, metronidazole




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Interleukin-4 in pg/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  2. Interleukin-5 in pg/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  3. IL-13 in pg/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  4. IL-10 in pg/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  5. IFN-Y in pg/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  6. TNF-α in pg/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  7. CCL11 in pg/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  8. Interleukin-6 in pg/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  9. C4bc u/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  10. C3bc u/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  11. iC3b u/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  12. C5a ng/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  13. C5b-9 u/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  14. C3a in ng/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  15. FXIIa activity in OD [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  16. FXIa in OD [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  17. FXIIa- C1-inhibitor complexes u/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  18. kallikrein-C1-inhibitor complexes u/ml [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  19. high-molecular weight kininogen in AU [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]
  20. thrombin-antithrombin complexes in ng/ml. [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]

Other Outcome Measures:
  1. C1-inhibitor activity in bronchoalveolar lavage [ Time Frame: 7 hours after bronchial instillation of HDM and LPS ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03051698


Locations
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Netherlands
Academic Medical Center
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
Sponsors and Collaborators
T. van der Poll
ZonMw: The Netherlands Organisation for Health Research and Development
Sanquin Plasma Products BV
Investigators
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Principal Investigator: Tom vd Poll, Prof, dr, MD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Publications:
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Responsible Party: T. van der Poll, Prof. dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT03051698    
Other Study ID Numbers: 2015_024
First Posted: February 14, 2017    Key Record Dates
Last Update Posted: June 24, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by T. van der Poll, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
C1-inhibitor
house dust mite
complement system
Additional relevant MeSH terms:
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Asthma
Angioedemas, Hereditary
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Angioedema
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, Inborn
Urticaria
Skin Diseases, Vascular
Skin Diseases
Anti-Bacterial Agents
Metronidazole
Vancomycin
Ciprofloxacin
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors