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ISRCTN
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ISRCTN55161632
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ClinicalTrials.gov identifier
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Public title
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Detection of novel genetic variants within the aquaporins 1 and 5
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Scientific title
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Detection of novel genetic polymorphisms (single nucleotide polymorphisms [SNPs]) within the aquaporins 1 and 5: an observational single-centre study
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Acronym
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N/A
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Serial number at source
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N/A
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Study hypothesis
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We hypothesised that single nucleotide polymorphisms (SNPs) within the aquaporins 1 and 5 contribute to the phenotypic variability of acute respiratory distress syndrome (ARDS), sepsis or bronchial asthma.
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Ethics approval
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Local ethics committee (Vorsitzender der Ethikkommission, Institut für Pharmakologie, Universitätsklinikum Essen) approved on the 9th December 2002 (ref: 01-97-1697, 05-2776, 06-3078, 07-3313)
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Study design
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Observational single-centre case-control study
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Countries of recruitment
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Germany
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Disease/condition/study domain
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Aquaporines, cell migration and inflammation
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Participants - inclusion criteria
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1. Acute respiratory distress syndrome:
1.1. Timing: acute onset
1.2. Oxygenation: partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ratio less than 200 mmHg (regardless of positive end expiratory pressure [PEEP])
1.3. Chest radiograph: bilateral infiltrates seen on frontal chest radiograph
1.4. Pulmonary artery wedge (PAW): less than 18 mmHg when measured or no clinical evidence of left atrial hypertension
2. Lung function testing with body plethysmography-revealed bronchial asthma
3. Patients with severe sepsis
4. Aged 18 to 70 years, both genders
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Participants - exclusion criteria
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No written informed consent is obtained
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Anticipated start date
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01/01/2005
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Anticipated end date
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01/01/2011
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Status of trial
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Ongoing |
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Patient information material
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Target number of participants
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200 healthy caucasian subjects, 150 ARDS-, 200 sepsis- and 100 bronchial asthma patients
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Interventions
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The following analyses will be performed on each participant:
1. Deoxyribonucleic acid (DNA) extraction from rest material of the routine diagnostic, e.g., saliva, urine or blood
2. Identification of novel DNA polymorphisms through sequencing polymerase chain reaction (PCR) products of the AQP1 and 5 promoter. The method of "slowdown PCR" should be used to amplify promoter fragments with extremely high GC content (greater than 85%).
3. Determination of transcriptional activity of haplotypes by reporter assays in different cell lines
4. Haplotype-dependent analysis of radiation and chemotherapeutics on cell proliferation in cell systems
5. Haplotype-dependent analysis of messenger ribonucleic acid (mRNA) level by quantitative real time PCR
6. Haplotype-dependent analysis of protein level by Western Blot
7. Haplotype-dependent analysis of cell migration
8. Haplotype-dependent analysis of transcription factors which bind to the polymorphic regions by electrophoretic mobility shift assay (EMSA)
9. Genotyping of ARDS, sepsis, bronchial asthma patients and healthy caucasian subjects by restriction fragment length polymorphism (RFLP) and pyrosequencing and haplotype-dependent analysis of survival and disease course using SPSS and GraphPad Prism software
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Primary outcome measure(s)
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Detection of SNPs wthin the Aqquaporin 1 and 5 gen which contribute to the phenotypic variability of ARDS, sepsis and bronchial asthma, measured at 30 day survival and 100 day survival
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Secondary outcome measure(s)
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Analysis of survival, disease course and rehabilitation, measured at 30 day survival and 100 day survival
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Sources of funding
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German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany) - pending as of 06/05/2009
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Trial website
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Publications
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2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18846354
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Contact name
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Dr
Michael
Adamzik
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Address
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Klinik fur Anasthesiologie und Intensivmedizin
Hufelandstrasse 55
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City/town
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Essen
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Zip/Postcode
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45122
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Country
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Germany
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Sponsor
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German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany)
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Address
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c/o Dr Simone Mueller
Lebenswissenschaften 1
Geschaftsstelle
Kennedyallee 40
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City/town
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Bonn
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Zip/Postcode
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53170
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Country
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Germany
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Sponsor website:
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http://www.dfg.de/
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Date applied
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06/05/2009
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Last edited
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03/07/2009
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Date ISRCTN assigned
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03/07/2009
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