C1-inhibitor in Allergic ASThma Patients

NCT03051698 | Terminated Phase 4

• 1 other identifier: 2015_024
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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

Conditions

Asthma

Keywords

C1-inhibitor; house dust mite; complement system

Outcome Measures

Primary Outcomes (1)

• Influx of inflammatory cells in the lung

  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 Outcomes (20)

• Interleukin-4 in pg/ml.

  7 hours after bronchial instillation of HDM and LPS

• Interleukin-5 in pg/ml.

  7 hours after bronchial instillation of HDM and LPS

• IL-13 in pg/ml.

  7 hours after bronchial instillation of HDM and LPS

• IL-10 in pg/ml.

  7 hours after bronchial instillation of HDM and LPS

• IFN-Y in pg/ml.

  7 hours after bronchial instillation of HDM and LPS

Other Outcomes (1)

• C1-inhibitor activity in bronchoalveolar lavage

  7 hours after bronchial instillation of HDM and LPS

Study Arms (3)

C1-inhibitor

EXPERIMENTAL

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

Drug: C1-inhibitor

Saline

PLACEBO COMPARATOR

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

Other: Saline

Antibiotics

EXPERIMENTAL

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

Drug: Antibiotics

Interventions

C1-inhibitor DRUG

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

Also known as: Cinryze

C1-inhibitor

Saline OTHER

0.9% NaCl

Saline

Antibiotics DRUG

vancomycin, ciprofloxacin, metronidazole

Also known as: vancomycin, ciprofloxacin, metronidazole

Antibiotics

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• T. van der Poll: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Prothya Biosolutions: collaborator

Study Sites (1)

Academic Medical Center

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Related Publications (7)

• Zeerleder S. C1-inhibitor: more than a serine protease inhibitor. Semin Thromb Hemost. 2011 Jun;37(4):362-74. doi: 10.1055/s-0031-1276585. Epub 2011 Jul 30.

  PMID: 21805442 BACKGROUND

• Zhang X, Kohl J. A complex role for complement in allergic asthma. Expert Rev Clin Immunol. 2010 Mar;6(2):269-77. doi: 10.1586/eci.09.84.

  PMID: 20402389 BACKGROUND

• Schmudde I, Laumonnier Y, Kohl J. Anaphylatoxins coordinate innate and adaptive immune responses in allergic asthma. Semin Immunol. 2013 Feb;25(1):2-11. doi: 10.1016/j.smim.2013.04.009. Epub 2013 May 19.

  PMID: 23694705 BACKGROUND

• de Boer JD, Berger M, Majoor CJ, Kager LM, Meijers JC, Terpstra S, Nieuwland R, Boing AN, Lutter R, Wouters D, van Mierlo GJ, Zeerleder SS, Bel EH, van't Veer C, de Vos AF, van der Zee JS, van der Poll T. Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial. Eur Respir J. 2015 Dec;46(6):1636-44. doi: 10.1183/13993003.00459-2015. Epub 2015 Sep 17.

  PMID: 26381519 BACKGROUND

• Bel EH. Mild asthma. N Engl J Med. 2013 Dec 12;369(24):2362. doi: 10.1056/NEJMc1313111. No abstract available.

  PMID: 24328483 BACKGROUND

• Krug N, Tschernig T, Erpenbeck VJ, Hohlfeld JM, Kohl J. Complement factors C3a and C5a are increased in bronchoalveolar lavage fluid after segmental allergen provocation in subjects with asthma. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1841-3. doi: 10.1164/ajrccm.164.10.2010096.

  PMID: 11734433 BACKGROUND

• Van Engelen TSR, Yang J, Haak BW, Bonta PI, Van Der Poll T, Wiersinga WJ; CAST study group. Gut Microbiome Modulation by Antibiotics in Adult Asthma: A Human Proof-of-Concept Intervention Trial. Clin Gastroenterol Hepatol. 2022 Jun;20(6):1404-1407.e4. doi: 10.1016/j.cgh.2021.07.030. Epub 2021 Jul 22.

  PMID: 34303860 DERIVED

MeSH Terms

Conditions

Asthma; Angioedemas, Hereditary

Interventions

Complement C1 Inhibitor Protein; SERPING1 protein, human; Sodium Chloride; Anti-Bacterial Agents; Vancomycin; Ciprofloxacin; Metronidazole

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Glycopeptides; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Tom vd Poll, Prof, dr, MD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: February 7, 2017
• First Posted: February 14, 2017
• Study Start: November 16, 2016
• Primary Completion: October 23, 2019
• Study Completion: October 23, 2019
• Last Updated: June 24, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)