Condition category
Respiratory
Date applied
15/09/2007
Date assigned
19/10/2007
Last edited
19/10/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Stephan Urs Sixt

ORCID ID

Contact details

Klinik fur Anasthesiologie und Intensivmedizin
Hufelandstrasse 55
Essen
45122
Germany

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

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 measures

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

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

http://www.dfg.de/

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

Results - basic reporting

Publication summary

Initial findings at http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17220374

Publication citations

  1. 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.

Additional files

Editorial Notes