This research proposal aims to assess the anti-inflammatory effects after 6 weeks treatment with tiotropium compared to placebo in patients with stable COPD.
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
A decrease of the amount of interleukin-6 en interleukin-8 proteins in
induced sputum will be the main parameter for assessing the anti-inflammatory
effects of 6 week treatment with tiotropium in patients with stable COPD.
Secondary outcome
Additionally, changes in sputum cell differentials and other cytokine
parameters (protein, mRNA,LTB4), blood cell differentials, CRP, and cytokine
parameters, health related quality of life (CCQ, CAT) will be assessed as well
as changes in post-bronchdilator FEV1.
Background summary
Acetylcholine is the primary parasympathetic neurotransmitter in the airways,
and induces bronchoconstriction. Since the cholinergic tone appears to be the
major reversible component of obstruction, muscarinic receptor antagonism and
bronchodilation represent the primary goal of anticholinergic therapy in
patients with COPD. Long-acting anticholinergic therapy is central in GOLD
stage B-D, because of improvements in lung function, quality of life, and
especially reduction of exacerbations. The elicited reduction in exacerbations
with the LAMA tiotropium appears larger than that of the LABA salmeterol even
when the bronchodilation is similar. These effects on exacerbation frequency
suggest that tiotropium might exert anti-inflammatory effects in the airways
next to bronchodilatory effects. This has been proven in animal models
Such an anti-inflammatory effect of anticholinergic intervention could be
clinically relevant; however it has not been previously demonstrated in
patients with COPD.
We hypothesize that tiotropium bromide reduces the ongoing inflammation in
patients with COPD compared to placebo. We expect a decrease of the amount of
interleukine-6 en interleukine-8 proteins in induced sputum after treatment
with tiotropium bromide
Study objective
This research proposal aims to assess the anti-inflammatory effects after 6
weeks treatment with tiotropium compared to placebo in patients with stable
COPD.
Study design
This will be a parallel design randomized controlled double-blinded study.
Intervention
COPD patients will be randomized to the treatment group (Tiotropium Respimat )
or to the placebo group.
Study burden and risks
It is not expected that subjects will receive any major individual benefit from
participation in this study. The study also has no major risks. Minor risks for
participants in this study are: 1) blood collection may cause bruising; 2)
sputum induction can lead to transient bronchoconstriction; 3) Tiotropium
Respimat may cause mild side effects, most notably dry mouth. It has been a
major drug for this indication already for more than 10 years in most countries
worldwide.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
•Men or women, age >= 40 years
•post-bronchodilator FEV1 >= 0.8 Litres
•smoking history of > 10 pack years.
•Being in a stable phase of COPD, as judged by the investigator. No courses of
systemic steroids last 4 weeks
•Post-bronchodilator FEV1 / FVC ratio < 70% and post-bronchodilator FEV1 <
80%pred.
Exclusion criteria
•Treatment with long-acting anticholinerigcs <4 weeks before the start of the
study.
•Treatment with corticosteroids <4 weeks before the start of the study.
•Concomitant diagnosis of asthma.
•Females of childbearing potential without an efficient contraception unless
they meet the following definition of post-menopausal: 12 months of natural
(spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH
>40 mIU/mL or the use of one or more of the following acceptable methods of
contraception:
a) Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).
b) Hormonal contraception (implantable, patch, oral, injectable).
c) Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/cream/suppository.
d) Continuous abstinence.
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 | EUCTR2018-002173-22-NL |
| CCMO | NL65946.042.18 |