The study the influence of two different inhalationflow manoeuvres on the lungdeposition in patients with cystic fibrosis categorized to patientgroups varying in FEV1 longfunction value and age.
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Congenital respiratory tract disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Lungdeposition: percentage of total lung deposition, aerosol penetration index
and homogeneity in aerosol distribution.
Secondary outcome
Tobramycin serum levels after inhalation. Serum samples will be used to
determine the tobramycin absorption kinetics, Cmax and Tmax will be determined.
The total lungdeposition will be measured not only by activity counts but also
by analysis of a 24 hours urine collection sample.
Background summary
Nebulation of antibiotics is a substantial part of CF therapy. Patient
characteristics as longstructure, FEV1 value, inhalationflow and inhalation
pattern together with nebulation device- and physical-chemical nebulation fluid
characteristics determine lungdeposition and clinical response.
Daily therapy can be improved if inhalation flow and aerosol droplet size can
be optimised for better lungdeposition in patients who differ in FEV1
lungfunction and age. The ratio between inhalation flow and aerosol droplet
size for different CF patientgroups are still unknown, just like the desired
site for tobramycin deposition in the lungs.
In this investigation a nebuliser is used, which is able to generate aerosol in
a reproducible matter. Both normal tidal breathing and a long and deep
inhalation mode are being supported by this nebuliser to investigate the
influence on CF lungdeposition in patients with different FEV1 values.
SPECT-CT gamma scinitgraphy is used for three dimensional radiotracer
quantification in regional lungstructures. Lungventilation is imaged for better
interpretation of aerosol deposition information. Furthermore a pharmacokinetic
tobramycin serum level profile will be determined after inhalation.
Essential information about optimizing nebulation therapy is needed, because
next generation nebulation therapeutics demand higher requirements to site of
deposition and nebulation efficiency.
Study objective
The study the influence of two different inhalationflow manoeuvres on the
lungdeposition in patients with cystic fibrosis categorized to patientgroups
varying in FEV1 longfunction value and age.
Study design
This study consists out of two study days.
On day one tobramycin aerosol deposition admixed with a radiotracer is
evaluated after nebulation in normal tidal breathing mode (TBM) or either a
slow and deep inhalation (TIM). This sequence is detemined by randomisation on
the first study day.
Before the SPECT-CT gamma scintigraphy survey of the lungdeposition in regional
lungstructures, lungfunction measurements and lungventilation will be
investigated. Tobramycin serum levels after inhalation will be taken on 0.25,
0.5, 1, 1.5, 2, 3, 4 hours after inhalation.
Urine will be collected till 24 hours after inhalation. The patient will be
asked to collect his or her urine outside the hospital in a urine container.
The 24 hours urine sample will be picked up at the patients home.
On study day two, minimal one week after the first study day, this procedure
(lung function measurement, lung ventilation imaging, aerosol deposition
imaging and tobramycin serum and urine level determination) is repeated.
On this study day patients will be asked to inhale a radiotracer containing
tobramycin aerosol, in the same dose, by an inhalationmode that differs from
the first study day either TIM or TBM.
In this study 18 patients with CF are included, categorized in three groups by
their FEV1 value; FEV1 40-60%, FEV1 60-80% and FEV1 80-100%.
Study burden and risks
Patients who participate in this study will be asked to visit both study days.
The following aspects of the study can be demanding or strenous
-Longfunction test: for some patients
-Tobramycin inhalation: bronchospasms or dyspnea
-Tc-DTPA radiotracer inhalation
-venflon canula, sensitive/ painfull site near canula
- painfull fingertip
Serum samples will be collected at 0.25, 0.5, 1, 1.5, 2, 3, 4 hours after
inhalation. Urine will be collected over 24 hours after inhalation.
Compared to other diagnostic procedures in nuclear medicine and radiology the
total radiation burden in this study is 3.52 mSv, 1.76 mSv for both study days,
and can be mentioned as relatively low. Participating patients on the short
term have no direct benefit in their daily therapy by this study. Although this
study is proposed to give more information about nebulation therapy, a
substantial part of the treatment of Cystic Fibrosis. The more because three
dimensional lung deposition imaging will be quantified in regional
structures.
Next generation nebulation medication (gene vectors and antibiotics) require
higher efficiency of the nebulation process, so better insight is needed.
Escamplaan 900
2504 AC Den Haag
NL
Escamplaan 900
2504 AC Den Haag
NL
Listed location countries
Age
Inclusion criteria
Clinical diagnosis cystic fibrosis
stable of disease
routine use of tobramycin
Exclusion criteria
pregnancy and lactation
acute exacerbation of pulmonary infection
use of any treatment before the start of the study that may interfere with the study
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 | EUCTR2007-001853-24-NL |
| CCMO | NL17265.098.07 |