Extracellular proteasome in the alveolar space: characterisation and function under physiological and pathophysiological condition
| ISRCTN | ISRCTN20709647 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN20709647 |
| Secondary identifying numbers | N/A |
- Submission date
- 15/09/2007
- Registration date
- 19/10/2007
- Last edited
- 18/09/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Stephan Urs Sixt
Scientific
Scientific
Klinik fur Anasthesiologie und Intensivmedizin
Hufelandstrasse 55
Essen
45122
Germany
Study information
| Study design | This study is an observational, single-centre study. The aim of this study is the description and characterisation of the extracellular alveolar proteasome in healthy and sick subjects. |
|---|---|
| Primary study design | Observational |
| Secondary study design | Case-control study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Scientific title | Extracellular proteasome in the alveolar space: characterisation and function under physiological and pathophysiological condition: an observational study |
| Study acronym | ALIHD |
| Study objectives | We hypothesised that 20S proteasome is present and functional in the extracellular alveolar space of healthy subjects and patients with Acute Respiratory Distress Syndrome (ARDS), sarcoidosis and in the alveolar space after lung transplantation in humans. |
| Ethics approval(s) | Ethics approval received from the local ethics committee (Vorsitzender der Ethikkommission, Institut für Pharmakologie, Universitätsklinikum Essen) on the 9th December 2002 (ref: 01-97-1697). |
| Health condition(s) or problem(s) studied | Extracellular proteasome in the alveolar space |
| Intervention | Healthy caucasians subjects and patients with ARDS, sarcoidosis and patients after lung transplantation were included after approval of the local ethics committee and informed written consent. Observational trial: Proteasomal activity will be measured in Broncho-Alveolar Lavage (BAL) supernatant from healthy subjects, patients with acute respiratory distress syndrome and lung transplantation using specific proteasomal fluorogenic substrates and I125 albumin, with and without specific proteasome inhibitors. After that the different enzyme activities of the study groups were compared with healthy subjects. Furthermore, gel filtration, western blot technique, Enzyme-Linked Immuno-Sorbent Assay (ELISA) and mass spectrometry, were applied for proteasome characterisation in the different study groups. |
| Intervention type | Other |
| Primary outcome measure | 1. Enzyme activity using specific proteasomal fluorogenic substrates and I125 albumin, with and without specific proteasome inhibitors 2. Detection of 20S proteasome with polyclonal antibody (western-blot) 3. Detection of immunoproteasome with LMP2 and LMP7 antibody (western-blot) 4. Gel filtration to evaluate the molecular weight of the extracellular proteasome in the bronchoalveolar space 5. Mass spectrometry of the gel filtration revealed hydrolysing activity and ELISA technique for the amount of extracellular, alveolar proteasome |
| Secondary outcome measures | No secondary outcome measures |
| Overall study start date | 01/01/2003 |
| Completion date | 01/01/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 70 Years |
| Sex | Both |
| Target number of participants | 300 subjects, including healthy subjects and patients with acute respiratory distress syndrome, sarcoidosis and lung transplantation. |
| Key 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. Sarcoidosis 3. Lung transplantation: patient after lung transplantation were lavaged in a routine diagnostic, for the screening of organ rejection and infection 4. Aged 18 to 70 years, both genders |
| Key exclusion criteria | 1. Acute respiratory distress syndrome: contraindication against bronchoscopy 2. Sarcoidosis: contraindication against bronchoscopy 3. Lung transplantation: contraindication against bronchoscopy 4. Healthy subjects: 4.1. Contraindication against bronchoscopy 4.2. Any lung diseases 4.3. Infection 4.4. Sepsis 4.5. Coronary heart disease |
| Date of first enrolment | 01/01/2003 |
| Date of final enrolment | 01/01/2008 |
Locations
Countries of recruitment
- Germany
Study participating centre
Klinik fur Anasthesiologie und Intensivmedizin
Essen
45122
Germany
45122
Germany
Sponsor information
German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany)
Research council
Research council
c/o Dr. Simone Mueller
Lebenswissenschaften 1
Geschaftsstelle
Kennedyallee 40
Bonn
53170
Germany
| Website | http://www.dfg.de/ |
|---|---|
"ROR" |
https://ror.org/018mejw64 |
Funders
Funder type
Research council
German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany) (ref: PE 301/4-1) - submitted
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Interim results article | initial findings | 01/05/2007 | Yes | No | |
| Results article | additional results | 01/10/2014 | Yes | No |
Editorial Notes
18/09/2017: Publication reference added.
