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C1-inhibitor in Allergic ASThma Patients (CAST)

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ClinicalTrials.gov Identifier: NCT03051698
Recruitment Status : Recruiting
First Posted : February 14, 2017
Last Update Posted : February 7, 2018
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Sanquin
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)
Estimated Enrollment : 60 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
Estimated Primary Completion Date : November 16, 2018
Estimated Study Completion Date : November 16, 2018

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

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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


Contacts
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Contact: Jack Yang, MD +31205665247 j.yang@amc.uva.nl

Locations
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Netherlands
Academic Medical Center Recruiting
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
Contact: Tom van der Poll, Prof.       t.vanderpoll@amc.uva.nl   
Contact: Jack Yang, MD       j.yang@amc.uva.nl   
Principal Investigator: Tom van der Poll, Prof.         
Sponsors and Collaborators
T. van der Poll
ZonMw: The Netherlands Organisation for Health Research and Development
Sanquin
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     History of Changes
Other Study ID Numbers: 2015_024
First Posted: February 14, 2017    Key Record Dates
Last Update Posted: February 7, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Lung Diseases, Obstructive
Lung Diseases
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Anti-Bacterial Agents
Metronidazole
Vancomycin
Ciprofloxacin
Antibiotics, Antitubercular
Complement C1 Inhibitor Protein
Anti-Infective Agents
Antitubercular Agents
Antiprotozoal Agents
Antiparasitic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs