AsthmaPhase 4CASTNCT03051698
C1-inhibitor in Allergic ASThma Patients
A Phase 4 study testing C1-inhibitor, Saline and Antibiotics in people with Asthma, run by T. van der Poll at 1 site in Netherlands.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Asthma
- What is being tested?
- C1-inhibitor, Saline and Antibiotics
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteNetherlands
- Study dates
- 16 Nov 2016to 23 Oct 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academic Medical Center
Amsterdam, North Holland, 1105 AZ
About this study
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
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
Read the 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.
- Conditions
- Asthma
- Being tested
- C1-inhibitor, Saline, Antibiotics
- Keywords
- C1-inhibitor, house dust mite, complement system
- Medical subject headings
- Asthma, Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1-inhibitorDrug
Also called Cinryze
100 Unit/kg IV, one gift prior to broncho provocation.
SalineOther
0.9% NaCl
AntibioticsDrug
Also called vancomycin, ciprofloxacin, metronidazole
vancomycin, ciprofloxacin, metronidazole
| Study group | Role | What they receive |
|---|---|---|
| C1-inhibitor | Experimental | One gift of intravenous administration of C1-inhibitor (Cinryze, 100U/kg) during one hour Receives: Drug: C1-inhibitor |
| Saline | Placebo comparator | One gift of intravenous administration of 0.9% NaCl during one hour. Receives: Other: Saline |
| Antibiotics | Experimental | broad spectrum antibiotics (vancomycin, ciprofloxacin, metronidazole) for 7 days (washout 36 hours before study day). Receives: Drug: Antibiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Influx of inflammatory cells in the lung
Most important cell types are the eosinophils and neutrophils in bronchoaveolar fluid
Measured: 7 hours after bronchial instillation of house dust mite (HDM) and lipopolyssacharide(LPS)
Secondary outcomes (20)
Interleukin-4 in pg/ml.
Measured: 7 hours after bronchial instillation of HDM and LPS
Interleukin-5 in pg/ml.
Measured: 7 hours after bronchial instillation of HDM and LPS
IL-13 in pg/ml.
Measured: 7 hours after bronchial instillation of HDM and LPS
IL-10 in pg/ml.
Measured: 7 hours after bronchial instillation of HDM and LPS
IFN-Y in pg/ml.
Measured: 7 hours after bronchial instillation of HDM and LPS
TNF-α in pg/ml.
Measured: 7 hours after bronchial instillation of HDM and LPS
CCL11 in pg/ml.
Measured: 7 hours after bronchial instillation of HDM and LPS
Interleukin-6 in pg/ml.
Measured: 7 hours after bronchial instillation of HDM and LPS
C4bc u/ml
Measured: 7 hours after bronchial instillation of HDM and LPS
C3bc u/ml
Measured: 7 hours after bronchial instillation of HDM and LPS
iC3b u/ml
Measured: 7 hours after bronchial instillation of HDM and LPS
C5a ng/ml
Measured: 7 hours after bronchial instillation of HDM and LPS
C5b-9 u/ml.
Measured: 7 hours after bronchial instillation of HDM and LPS
C3a in ng/ml
Measured: 7 hours after bronchial instillation of HDM and LPS
FXIIa activity in OD
Measured: 7 hours after bronchial instillation of HDM and LPS
FXIa in OD
Measured: 7 hours after bronchial instillation of HDM and LPS
FXIIa- C1-inhibitor complexes u/ml
Measured: 7 hours after bronchial instillation of HDM and LPS
kallikrein-C1-inhibitor complexes u/ml
Measured: 7 hours after bronchial instillation of HDM and LPS
high-molecular weight kininogen in AU
Measured: 7 hours after bronchial instillation of HDM and LPS
thrombin-antithrombin complexes in ng/ml.
Measured: 7 hours after bronchial instillation of HDM and LPS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2017
- Study start16 Nov 2016
- Primary completion23 Oct 2019
- Study completion23 Oct 2019
Why it stopped: Interim analysis showed no differences between groups
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- T. van der Poll
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, Prothya Biosolutions
- Responsible party
- Sponsor-investigator, T. van der Poll, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Tom vd Poll, Prof, dr, MD, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03051698
- Sponsor's protocol ID
- 2015_024
- Acronym
- CAST
- Status last verified
- Jun 2020
- First submitted
- 7 Feb 2017
- Last updated
- 24 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21805442Zhang 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.
PubMed 20402389Schmudde 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.
PubMed 23694705de 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.
PubMed 26381519Bel EH. Mild asthma. N Engl J Med. 2013 Dec 12;369(24):2362. doi: 10.1056/NEJMc1313111. No abstract available.
PubMed 24328483Krug 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.
PubMed 11734433Van 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.
PubMed 34303860
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03051698
- Acronym / sponsor ID
- CAST / 2015_024
- Conditions
- Asthma
- Keywords
- C1-inhibitor, house dust mite, complement system
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim analysis showed no differences between groups
- Enrolment
- 37 participants (actual)
- Lead sponsor
- T. van der PollUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, Prothya Biosolutions
- Study start
- 16 Nov 2016 (actual)
- Primary completion
- 23 Oct 2019 (actual)
- Study completion
- 23 Oct 2019 (actual)
- First posted
- 14 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| C1-inhibitor | Experimental | Drug: C1-inhibitorOne gift of intravenous administration of C1-inhibitor (Cinryze, 100U/kg) during one hour |
| Saline | Placebo comparator | Other: SalineOne gift of intravenous administration of 0.9% NaCl during one hour. |
| Antibiotics | Experimental | Drug: Antibioticsbroad spectrum antibiotics (vancomycin, ciprofloxacin, metronidazole) for 7 days (washout 36 hours before study day). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (9 listed)
- 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]
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| C1-inhibitorAlso: Cinryze100 Unit/kg IV, one gift prior to broncho provocation. | Drug | C1-inhibitor |
| Saline0.9% NaCl | Other | Saline |
| AntibioticsAlso: vancomycin, ciprofloxacin, metronidazolevancomycin, ciprofloxacin, metronidazole | Drug | Antibiotics |
Primary outcome
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
20 secondary outcomes
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
Results and safety
The study was stopped early (reason given: Interim analysis showed no differences between groups). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2020.
- Background: PubMed 21805442Zeerleder 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.
- Background: PubMed 20402389Zhang 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.
- Background: PubMed 23694705Schmudde 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.
- Background: PubMed 26381519de 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.
- Background: PubMed 24328483Bel EH. Mild asthma. N Engl J Med. 2013 Dec 12;369(24):2362. doi: 10.1056/NEJMc1313111. No abstract available.
- Background: PubMed 11734433Krug 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.
- Derived from this study: PubMed 34303860Van 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tom vd Poll, Prof, dr, MD principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing C1-inhibitor, Saline and Antibiotics in people with Asthma, run by T. van der Poll at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Interim analysis showed no differences between groups). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Influx of inflammatory cells in the lung (time frame: 7 hours after bronchial instillation of house dust mite (HDM) and lipopolyssacharide(LPS)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03051698, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2020.