Effect of Azithromycin on Fatty Acids in CF

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Azithromycin on Lipoproteins and Docosahexaenoic Acid in Patients With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Azithromycin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: CF patients receive for 4 weeks Azithromycin. Study measures are assessed before and after 4 weeks
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azithromycin<br>oral Azithromycin 10 mg/kg Body weight, max. 500 mg every Monday, Wednesday and Friday for 4 weeks | Drug: Azithromycin<br> <br> * Other names: Zithromax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipoproteins in Serum (after overnight fast) | VLDL,LDL,HDL, Cholesterin | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | 
| Fatty acids in EDTA-Plasma and erythrocyte membranes (after overnight fast) | linol acid, arachidon acid, Alpha linolen acid, eicosapentaen acid, Docoshexaen acidsdocosahexaen acid | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokines in induced sputum and whole blood | Lipopolysaccharid binding Protein (LBP), interleukin-8 (IL-8) und Tumor necrosis factor Alpha (TNF Alpha) | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | 
| ICAM1 (Serum) |  | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | 
| 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 | Clinical score | Day 0 | 
| Body weight, length |  | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | 
| Lung function test | VC, FEV1, MEF 25 | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | 
| Nutrition protocol | Evaluation of Food intake and calculation of fat composition, Protein etc. | For 7 days before day 0 and day 28 | 
| Resolvins in EDTA plasma |  | Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cystic fibrosis