We will investigate the local and systemic effects of carbon nanoparticles on inflammation and coagulation in humans by bronchial segmental challenge
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Neutrophil, eosinophil and mast cell responses in blood and bronchoalveolar
lavage fluid (BALF):
* Total leukocyte counts and differentials
* Neutrophil response (LTB4, myeloperoxidase (MPO))
* Eosinophil response (eosinophil cationic protein (ECP))
* Mast cell response (chymase, tryptase)
Activation of cytokine- and chemokine network :
* Proinflammatory cytokines: TNF-*, IL-5, IL-6, IL-17, VEGF, c-kit ligand,
* Anti-inflammatory cytokines : IL-10
* CXC chemokines: IL-8, GRO-*, IP-10
* CC chemokines: MCP-1, MIP-1*, MIP-1*
General: C-reactive protein measurement
Secondary outcome
Activation of coagulation and fibrinolysis (BALF and/or blood):
* Coagulation: TAT complexes, F1+2 prothrombin fragment, soluble tissue factor,
D-dimers
* Fibrinolysis: PA activity, tPA, PAI-1, PAP complexes
* Anticoagulant proteins: protein C, activated protein C, antithrombin, soluble
thrombomodulin
Amino acid pattern in exhaled breath condensate
Metabolomic fingerprint as obtained by Liquid chromatography-mass spectrometry
(LC-MS)
Lung functions will be assessed before and after the provocations.
Background summary
Multiple epidemiologic studies have shown a strong association between exposure
to particulate matter (PM) as part of air pollution and increased morbidity and
mortality due to cardiovascular and pulmonary events. Particulate matter is
derived by incomplete combustion of motor fuel and consists of a complex
mixture of different types and variably sized particles. Nanoparticles have a
diameter of less than 0.1 *m. Because of their higher deposition efficiency in
the pulmonary region and their ability to penetrate lung cells, they are likely
candidates for causing the pulmonary injury associated with particulate matter.
The specific effects of inhalation of carbon nanoparticles are largely unknown.
Study objective
We will investigate the local and systemic effects of carbon nanoparticles on
inflammation and coagulation in humans by bronchial segmental challenge
Study design
This is an investigator-initiated, randomized controlled, single centre, single
blinded, dose escalation study.
Intervention
Subjects will receive saline in one lungsegment and in the other lung they will
be challenged with also saline (placebo, n=8), saline with 10 *g carbon
nanoparticles (n=4), saline with 50 *g carbon nanoparticles (n=4) or saline
with 100 *g carbon nanoparticles(n=8).
Study burden and risks
The burden associated with this study includes a screening visit, during which
an intake interview, a physical examination, routine blood tests (40ml) and
lung function will be done. At the study day, all subjects will undergo two
bronchoscopies, which in our own experience from previous studies, as well as
based on literature is well tolerated. Each bronchoscopy will be preceded by a
blood draw (2 x 40 ml) and collection of exhaled breath condensate. Although
previous inhalation studies with particulate matter revealed no significant
risks or discomfort, bronchial instillation of carbon black nanoparticles may
induce bronchus obstruction. For this reason there will be close monitoring by
spirometry and salbutamol 100 *g will be available as rescue medication during
the study for all subjects.
Meibergdreef 9
1105 AZ
NL
Meibergdreef 9
1105 AZ
NL
Listed location countries
Age
Inclusion criteria
* Healthy male subjects between 18 and 45 years of age
* No clinically significant findings during physical examination and haematological and biochemical screening.
* Baseline FEV1 > than 80% of predicted value.
* No current smoking for at least 1 year and less than 5 pack years of smoking history
Exclusion criteria
* History of any relevant disease
* A history of smoking within the last 12 months, or regular consumption of greater than three units of alcohol per day
* Administration of any investigational drug within 30 days of study initiation
* Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation
* History of serious drug-related reactions, including hypersensitivity
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL35297.018.11 |