Cystic Fibrosis
Conditions
Keywords
cystic fibrosis
Brief summary
In collaboration with Dr.Birgit Alteheld, Institute of Nutrional Sciences of the university of Bonn, Germany the following effect is explored: Effect of a 4 week therapy with AZT on synthesis of lipoproteins as well as Docosahexaen and other fatty acids in patients with Cystic Fibrosis (CF). Moreover proinflammatory cytokines in blood and sputum are of interest.
Detailed description
The macrolide azithromycin (AZT) is recommended by Flume in the CF pulmonary Guidelines for long-term treatment of patients with CF chronically colonized with Pseudomonas aeruginosa due to its immunomodulating properties . AZT causes a significant reduction of the proinflammatory cytokine Lipopolysaccharid binding protein (LBP) according to Steinkamp and Schmitt-Grohé. There is an inverse correlation between LBP and lung function. Moreover Schmitt-Grohé and coworkers provided evidence of a positive correlation between the lipoprotein HDL and lung function. Ribeiro and coworkers found an increased expression of Lipid/Cholesterol genes of primary human airway epithelial cultures after treatment with AZT. Freedman and coworkers were able to show decreased levels of Docosahexaen acid in CF patients. The aim of this study is to explore the impact of a 4 week trial of AZT on lipoprotein and fatty acids (docosahexaen acid etc.) synthesis. Delta F508 homozygous patients receive AZT (10 mg/kg body weight resp. max 500 mg) every Monday, Wednesday and Friday for 4 weeks. 20 patients (age 10-60 years) will be recruited. Fatty acids (blood), cytokines (whole blood and induced sputum) and clinical parameters are assessed before and 4 weeks after AZT treatment.
Interventions
DRUGAzithromycin
Sponsors
University of Bonn
Goethe University
University Childrens' Hospital (Zentrum für Kinderheilkunde des Universitätsklinikum Bonn)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
CF patients receive for 4 weeks Azithromycin. Study measures are assessed before and after 4 weeks
Eligibility
Sex/Gender
ALL
Age
10 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Delta 508 homozygous and regularly visiting the CF outpatient clinic Bonn
Exclusion criteria
* clinical or laboratory signs (CRP \> 20 mg/L) of an exacerbation, * treatment with systemic steroids 14 days preceeding this trial * elevated liver function tests (\> twice normal range)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lipoproteins in Serum (after overnight fast) | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | VLDL,LDL,HDL, Cholesterin |
| Fatty acids in EDTA-Plasma and erythrocyte membranes (after overnight fast) | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | linol acid, arachidon acid, Alpha linolen acid, eicosapentaen acid, Docoshexaen acidsdocosahexaen acid |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Matrixmetalloprotease 9 (Serum) | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | — |
| WBC + CRP, IgE, RAST Aspergillus fum, ECP (Serum), Carotin, Vitamin E | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | — |
| Shwachman-Score | Day 0 | Clinical score |
| Cytokines in induced sputum and whole blood | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | Lipopolysaccharid binding Protein (LBP), interleukin-8 (IL-8) und Tumor necrosis factor Alpha (TNF Alpha) |
| Lung function test | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | VC, FEV1, MEF 25 |
| Nutrition protocol | For 7 days before day 0 and day 28 | Evaluation of Food intake and calculation of fat composition, Protein etc. |
| Resolvins in EDTA plasma | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | — |
| Body weight, length | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | — |
| ICAM1 (Serum) | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | — |
Outcome results
None listed