Intravenously administered rhAPC has protective effects on HDM-LPS induced allergic lung inflammation.
ID
Bron
Verkorte titel
Aandoening
Allergic asthma, house dust mite allergy, lung inflammation, coagulation
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
Influx, differentiation and possible phenotype differences of inflammatory cells.
Achtergrond van het onderzoek
Allergic lung inflammation is associated with reduced bronchoalveolar levels of endogenous activated protein C (APC). The biological effects of APC are pleiotropic, and can be roughly divided in anticoagulant and cytoprotective effects. Recombinant human Activated Protein C (rhAPC) has been shown to decrease inflammation and is known for its capability to decrease mortality of patients with severe sepsis. Recent evidence derived from animal studies, in part from our laboratory, indicates that APC is also beneficial in allergic inflammatory conditions. In this study, we will examine whether intravenous administration of rhAPC is capable to inhibit local inflammation, within a lung subsegment, induced by combined administration of house dust mite (HDM) and lipopolysaccharide (LPS) in asthma patients. LPS is a relevant in this context because it is abundant in the natural human environment (and a natural contaminant of HDM) and known to enhance HDM induced allergic inflammation in asthma patients. The primary objective of this study is to determine the effect of intravenously administered rhAPC on HDM-LPS induced allergic lung inflammation.
Doel van het onderzoek
Intravenously administered rhAPC has protective effects on HDM-LPS induced allergic lung inflammation.
Onderzoeksopzet
28 asthma patients will start on intravenous treatment with rhAPC or placebo 4 hours before (t = -4 hours) bronchial instillation of HDM/LPS in a lung subsegment and bronchial instillation of saline in a contralateral lung subsegment (t = 0 hours). Intravenous treatment with rhAPC or placebo will be continued until 1 hour before initiation of the second bronchoscopy.
Onderzoeksproduct en/of interventie
Intravenous rhAPC treatment and bronchoscopy allergen challenge and lavage. At 05:00 asthma patients will start on intravenous rhAPC treatment or placebo treatment. At 09:00 patients are challenged with housedustmite+LPS in one lungsegment and Saline in a lung segment of the contralateral lung. At 16.00 intravenous treatment is halted and at 17:00 a second bronchoscopy is done to lavage the segments.
Publiek
Academisch Medisch Centrum
Meibergdreef 9
Room F0-117
Amsterdam 1105 AZ
The Netherlands
+31 (0)20 5665247
j.d.deboer@amc.uva.nl
Wetenschappelijk
Academisch Medisch Centrum
Meibergdreef 9
Room F0-117
Amsterdam 1105 AZ
The Netherlands
+31 (0)20 5665247
j.d.deboer@amc.uva.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. Intermittent to mild asthmatics between 18 and 45 years of age according to the Global Initiative for Asthma (GINA) criteria;
2. Allergy for HDM documented by a positive RAST and a positive skin prick test;
3. No clinically significant findings during physical examination and hematological and biochemical screening;
4. At spirometry FEV1 more than 70% of predicted value;
5. Able to communicate well with the investigator and to comply with the requirements of the study;
6. Stable asthma without the use of asthma medication 2 weeks prior to the study day;
7. Written informed consent;
8. No current smoking for at least 1 year and less than 10 pack years of smoking history;
9. Both male and female subjects are eligible for the study. Female subjects of child bearing potential will use adequate anti-conceptive precautions and will be tested for pregnancy.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
1. Relevant comorbidity, pregnancy and/or recent surgical procedures;
2. A history of smoking within the last 12 months, or regular consumption of greater than three units of alcohol per day;
3. Exacerbation and/or the use of asthma medication within 2 weeks before start;
4. Administration of any investigational drug within 30 days of study initiation;
5. Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation;
6. History of enhanced bleeding tendency or abnormal clotting test results;
7. History of heparin-induced thrombocytopenia;
8. History of serious drug-related reactions, including hypersensitivity;
9. Inability to maintain stable without the use of asthma medication 2 weeks before start.
Opzet
Deelname
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
| Register | ID |
|---|---|
| NTR-new | NL2802 |
| NTR-old | NTR2943 |
| CCMO | NL36336.018.11 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |
| OMON | NL-OMON35983 |