Objective: The objective of the study is establish the half-life of eosinophils in blood and sputum and determination of the effect of Nucala® hereon.
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints: the main study parameter is enrichment of
2H-DNA in the DNA of eosinophils obtained at different time points after
labelling. The patients will be asked to drink 2H-glucose (1 g/kg) during 6 hrs
at time -5 days before the start of the treatment. After 5 days labelled
eosinophils will leave the bone marrow and the pulse of 2H-DNA can be followed
in blood and sputum. The kinetics of the pulse relates with the half-life of
the cells
Secondary outcome
The secundary parameters are:
1. Th17/Th2 cytokine profile in peripheral blood. Data will be determined by
multiplex technology (Luminex)
2. Profile of eosinophil degranulation products in sputum samples.
Background summary
Eosinophil asthma, particularly the steroid unresponsive form, benefits from
treatment with a monoclonal antibody (Mepolizumab/Nucala®) directed against
IL-5 (terminal differentiation factor of eosinophils) The underlying mechanism
is unclear as treatment with Nucala® needs > 6 months in order to establish a
significant clinical effect, whereas the effect on eosinophils in blood and
bone marrow is evident after 1-2 weeks.
Study objective
Objective: The objective of the study is establish the half-life of
eosinophils in blood and sputum and determination of the effect of Nucala®
hereon.
Study design
Study design: the study is double-blind placebo controlled intervention study.
Intervention
Intervention (if applicable): the intervention is treatment with Nucala® (100
mg subcutaneously every 4 weeks/4 doses) or with placebo (saline, every 4
weeks/4 doses).
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: the burden of the study is relatively high as
the patients are asked to come for two days to the UMCU for the labelling days
with 2H-glucose en for 10 visits for donation of blood (10 min) and 3 times
donation of induced sputum 30 min. The risks of the study are minimal: no
adverse effects has been linked to the treatment with Nucala® other than mild
and reversible symptoms such as common cold, headache, nasal congestion, back
pain and pyrexia. The labelling with 2H-glucose is safe as there has been no
documented negative effects at the dose that is used in the study. Both
venapunction and production of induced sputum are considered safe and cause
only mild discomfort. Induced sputum might induce a mild shortage of breath
that is easily treated with beta-2 agonists (bronchus dilators). The
eosinophilic asthma patients are chosen as they have sufficient numbers of
eosinophils in blood and sputum and Nucala® is registered for this patient
group.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
* Age > 18 and younger than 70 years
* Diagnosis of eosinophil asthma despite use of corticosteroids
* Suitable for sputum induction
* >2.5% sputum eosinophils OR blood eosinophils > 0.25x10^9/L
Exclusion criteria
* Any acute or chronic infection (eg. HIV, Hepatitis, STDs, pneumonia, influenza etc.)
* Insulin dependent diabetes
* Smoking at present or in the last 12 months and/or a past history of more than 10 pack years
* Proven allergic bronchopulmonary aspergillosis
* Auto-immune diseases
* Use of immune modulating medication (such as NSAID's, monoclonal antibodies, purine antagonistis etc.) excluding:
o Steroids used to treat asthma
* exuberant alcohol consumption (for males > 36 glasses per week, for females >24 glasses per week)
* Drug use
* Active cancer or a cancer diagnosed < 5 years ago.
* Unstable disease despite high dose of systemic steroids (20 mg prednisolon or more)
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2016-002014-52-NL |
| CCMO | NL57535.041.16 |