Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Extracellular proteasome in the alveolar space: characterisation and function under physiological and pathophysiological condition: an observational study
Acronym
ALIHD
Study hypothesis
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
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).
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
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
Condition
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
Phase
Not Specified
Drug names
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 trial start date
01/01/2003
Overall trial end date
01/01/2008
Reason abandoned (if study stopped)
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. 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
300 subjects, including healthy subjects and patients with acute respiratory distress syndrome, sarcoidosis and lung transplantation.
Participant 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
Recruitment start date
01/01/2003
Recruitment end date
01/01/2008
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) (ref: PE 301/4-1) - submitted
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
Basic results (scientific)
Publication list
1. 2007 initial findings in: https://www.ncbi.nlm.nih.gov/sites/17220374
2. 2014 additional results in https://www.ncbi.nlm.nih.gov/sites/25269709
Publication citations
-
Initial findings at
Sixt SU, Beiderlinden M, Jennissen HP, Peters J, Extracellular proteasome in the human alveolar space: a new housekeeping enzyme?, Am. J. Physiol. Lung Cell Mol. Physiol., 2007, 292, 5, L1280-8, doi: 10.1152/ajplung.00140.2006.