Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Detection of novel genetic polymorphisms (single nucleotide polymorphisms [SNPs]) within the aquaporins 1 and 5: an observational single-centre study
Acronym
Study hypothesis
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.
Ethics approval
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)
Study design
Observational single-centre case-control study
Primary study design
Observational
Secondary study design
Case-control study
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
Condition
Aquaporines, cell migration and inflammation
Intervention
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
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measures
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
Secondary outcome measures
Analysis of survival, disease course and rehabilitation, measured at 30 day survival and 100 day survival
Overall trial start date
01/01/2005
Overall trial end date
01/01/2011
Reason abandoned
Eligibility
Participant inclusion criteria
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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
200 healthy caucasian subjects, 150 ARDS-, 200 sepsis- and 100 bronchial asthma patients
Participant exclusion criteria
No written informed consent is obtained
Recruitment start date
01/01/2005
Recruitment end date
01/01/2011
Locations
Countries of recruitment
Germany
Trial participating centre
Klinik fur Anasthesiologie und Intensivmedizin
Essen
45122
Germany
Sponsor information
Organisation
German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany)
Sponsor details
c/o Dr Simone Mueller
Lebenswissenschaften 1
Geschaftsstelle
Kennedyallee 40
Bonn
53170
Germany
Sponsor type
Research council
Website
Funders
Funder type
Research council
Funder name
German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany) - pending as of 06/05/2009
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18846354
Publication citations
-
Results
Adamzik M, Frey UH, Bitzer K, Jakob H, Baba HA, Schmieder RE, Schneider MP, Heusch G, Peters J, Siffert W, A novel-1364A/C aquaporin 5 gene promoter polymorphism influences the responses to salt loading of the renin-angiotensin-aldosterone system and of blood pressure in young healthy men., Basic Res. Cardiol., 2008, 103, 6, 598-610, doi: 10.1007/s00395-008-0750-z.